Zeolite molecular sieves for the removal of toxins

ABSTRACT

Medical use of natural and synthetic zeolites for treatment, prevention, and palliation in humans or animals of deleterious concentrations of ammonia, mercaptans, heavy metals and other toxins by oral administration.

This application is based on U.S. Provisional Patent Application No.60/512,395, filed Oct. 20, 2003, the entire contents of which areincorporated herein by reference.

The present invention relates to methods and compositions for treating,preventing, and palliating elevated levels of certain toxins in humans.

Hepatic Encephalopathy Remains a Significant Health Problem

Predominantly because of the large degree of alcohol use in society,chronic liver disease progressing to cirrhosis remains a burdensomehealth problem. While other toxic liver insults are responsible to alesser degree, the final common pathway remains the same: progressivehepatic fibrosis and decrease in the proportion of metabolically activehepatocytes. These pathological changes result in systemic healtheffects related to poor detoxification of endogenously produced ammoniaand exogenously administered medications. Because of the cirrhoticliver's markedly reduced ability to neutralize and remove ammonia, anatural waste product from the metabolism of proteins, its blood levelrises causing a decreased ability for affected patients to mentate,sense and move normally. This decrease in these functions whenattributable to chronic liver disease is known as hepaticencephalopathy.

It is estimated that the economic burden to society related to just thecosts of hospitalization for chronic liver disease is over $1 billionannually in the United States. A large portion of these costs is thedaily charge for the hospital room; the average stay is approximately 6days. Thus, if an intervention could be developed that would decreasethe average length of hospital stay and/or diminish the need forpatients to be hospitalized, patients with chronic liver disease wouldbenefit and the economic burden to society would decrease.

Current standard of care includes the use of supportive care (hydration,vitamins, nutrition administered parenterally, treatment of anygastrointestinal bleeding,) and the drug lactulose, a non-absorbeddisaccharide that functions to decrease the rate of absorption of andincrease the rate of fecal elimination of ammonia. Lactulose, which issold as a crystalline powder in a single-dose plastic package, isinconvenient to use in the acute hospital setting because of the needfor suspension/dissolution in a sorbitol solution. Moreover, lactuloseis only modestly effective and does not appear to have been subjected torandomized controlled trials prior to receiving marketing approval bythe US Food and Drug Administration.

Lead Poisoning Remains a Significant Health Problem

Despite advances in the recognition and treatment of clinical andsubclinical lead poisoning, a large number of children in the UnitedStates are considered lead poisoned. Effective therapy exists forlowering blood lead levels, however the long-term adverse event risk ofthese treatments limit their use, especially at the lower levels ofblood lead.

As taught in a recent government publication (Eliminating Childhood LeadPoisoning: A Federal Strategy Targeting Lead Paint Hazards; President'sTask Force on Environmental Health Risks and Safety Risks to Children;Department of Health and Human Services and the Environmental ProtectionAgency; February, 2000) lead is most hazardous to the nation's 24million children under six years old of which approximately 4.4% or 1million have blood lead levels (BLL) >10 μg/dL. The spectrum andseverity of morbidity of lead poisoning increases as blood lead levelsincrease: reduced IQ, decreased hearing, decreased growth and behaviorproblems in children can be observed at BLL as low as 10 μg/dL, impairednerve function at 20 μg/dL, reduced vitamin D metabolism at 30 μg/dL,damage to hematopoiesis at 40 μg/dL, severe stomach cramps above 50μg/dL and severe brain damage, kidney damage and severe anemia between50 and 100 μg/dL. Based on epidemiological models and estimates, a childis estimated to lose 2 IQ (intelligence quotient) points for each 10μg/dL increase in blood lead level.

Current treatments include intravenous chelation therapy with EDTA(ethylenediamine tetraacetic acid) oral chelation therapy with drugssuch as succimer, penicillamine and British anti-Lewisite (BAL).Chelation therapy with EDTA is indicated for severe lead poisoning andmust be administered—either three times daily or as a continuousinfusion—in combination with succimer. Succimer, an oral drug, isadministered on a subchronic basis and is not indicated for BLL <20μg/dL. Penicillamine may also be used, but is known for a particularlytroublesome side effect profile, which limits its chronic use.Additional details are found below.

EDTA (edetate, versenate; CAS [62-33-9]) remains difficult to administerdespite its demonstrable lead-chelating activity. It remains a componentof standard of care for severe cases of lead poisoning where rapiddecrease in the BLL is desired and requires hospitalization. Keypharmacological properties of EDTA include only intravenousadministration and half-life of 20 to 60 minutes. Rapid clearanceresults in only one-half the drug remaining one hour followingadministration and only 5% of the administered dose remains after 24hours. The dose must be adjusted for decreased renal clearance.Substantial monitoring is required for cardiac changes, renal functionand serum electrolyte changes resulting in daily phlebotomy andattachment to a cardiac monitor. These precautions are recommendedbecause of potential decreases in serum zinc, copper and iron, which arealso chelated by EDTA. Because EDTA may only be administeredparenterally, local pain and swelling are a risk. Systemic adverseevents include fever, chills, malaise, nausea, vomiting, anorexia,myalgias, arthralgias and a histamine-like reaction. Nephrotoxicity canmanifest as acute tubular necrosis, microscopic hematuria, proteinuriaand elevated blood urea nitrogen and serum creatinine. The liver may beaffected as evidenced by transient mild elevations of the transaminasesand the bone marrow may also be affected as evidenced by the findings ofanemia and thrombocytopenia.

Succimer (CHEMET, dimercaptosuccinic acid, DMSA; CAS [304-55-2]) is awhite crystalline powder with an unpleasant odor and tastecharacteristic of mercaptans. It is administered orally in divided dosesbased on the size of the patient thereby making administration easierand not requiring hospitalization. It is indicated for blood leadlevels >45 μg/dL and is expressly not indicated for prophylaxis againstlead poisoning in a lead laden environment. It is effective in reducingthe blood lead level, although several features limit and complicate itsuse. It is recommended to administer succimer every 8 hours for thefirst 5 days followed by twice daily for the next 14 days. A waitingperiod is recommended before a second 19-day cycle should begin. Weeklymonitoring of the blood counts is recommended for proper management ofthe drug-induced neutropenia. If the absolute neutrophil count decreasesbelow 1200 /μL, succimer administration should stop until recoveryto >1500 /μL. Drug-induced elevations of liver transaminases, which aremild and transient and seen in up to 10% of patient, should be monitoredfor weekly. A particular toxicity in the form of recurrent mucocutaneouseruptions has been described and requires cessation of therapy. Systemicadverse events known with succimer administration include nausea,vomiting, diarrhea, anorexia, loose stools, metallic taste and occursingly or in combination in up to 12% of children and 21% of adults. Inaddition, back pain, abdominal cramps, chills and flu-like symptoms havebeen reported in 5% of children and 16% of adults. Succimer is known tointeract with various laboratory tests resulting in incorrect values ofurine ketones, uric acid and creatine phosphokinase activity.

Penicillamine (Cuprimine, D-Pen, beta,beta-dimethylcysteine,3-mercaptovaline; CAS [52-67-5]) is a chelating agent, which has foundutility in treating Wilson's disease, cystinuria and rheumatoidarthritis. It is a white, crystalline powder, which is freely soluble inwater. Penicillamine is known to interfere with normal tropocollagencross-linking resulting in newly formed collagen fibrils, which arecleaved. To achieve maximum bioavailability and avoid chelation ofmetals within ingested foods or vitamins, it is recommended thatpenicillamine be taken on an empty stomach 1 hour before or 2 hoursafter meals. Penicillamine is associated with a number of untowardreactions, which are potentially fatal. Serious blood dyscrasiasincluding fatal aplastic anemia and fatal agranulocytosis have beenobserved during chronic treatment and close monitoring of white bloodcount, white cell differential and hemoglobin are strongly recommendedby the manufacturer. Thrombocytopenia and eosinophilia are otherhematological effects observed. Routine analysis of the urine isrecommended to detect the insidious onset of proteinuria and microscopichematuria, which may be associated with the Goodpasture's syndrome.Other adverse effects include several of the described subtypes ofpemphigus (especially pemphigus foliaceous), increased skin friabilityat pressure points and sites of trauma, lupus-like syndrome (notassociated with hypcomplementemia) with elevated anti-nuclear antibody(ANA) titer, aphthous ulceration of the oral mucous membranes,myasthenia gravis and hypoguesia, or blunting of the sense of taste. Themanufacturer recommends close observation and frequent follow-up of anypatient receiving penicillamine.

Dimercaprol (BAL, British anti-lewisite, 2,3-dimercapto-1-propanol; CAS[59-52-9]) is a clear, colorless, viscous oily fluid with a pungent odortypical of mercaptans. It is dissolved in and administered,intramuscularly, in peanut oil. Its mechanism of action appears to becomplexation with and oxidation by heavy metal ions including lead,copper and arsenic. The dose administered is based on achieving a 2:1molar ratio of dimercaprol to the heavy metal and it may be used incombination with EDTA. The half-life is short such that followingintramuscular administration, dimercaprol is essentially all renallyexcreted within 4 hours. There are a number of pronounced anddose-related side effects which the amount or dimercaprol that may beadministered. Approximately 50% of patients administered the 5 mg/kgdose will experience one of several adverse events. Amongst the mostcommon of the side effects is a rise in systolic and diastolic bloodpressure by up to 50 mmHg. Nausea is commonly reported and to a lesserdegree vomiting. Headache is reported less commonly than nausea althoughfurther details about the headache are not described in the referencescited. A burning sensation in the lips, mouth and throat accompaniedwith the feeling of constriction is well known. Conjunctivitis,blepharospasm, lacrimation, rhinorrhea and increased salivation are alsoknown to be associated with dimercaprol use. Other less common sideeffects include tingling of the feet and hands, abdominal pain, sweatingof the forehead and hands and painful, sterile abscesses at theinjection sites. Dimercaprol is known to cause hemolysis in patientswith glucose-6-phosphate dehydrogenase deficiency and a transientdecrease in the percentage of polymorphonuclear leukocytes has beenobserved. The manufacturer recommends that the urine be alkalinized tomaintain the integrity of the metal-drug complex during transportthrough the renal tubule.

Although each of these interventions is effective at reducing theapparent blood level, following such therapy, it is well known thatthere is a rebound in the BLL, which arises from unchelated tissuestores such as the bone and soft tissues. There is at present noFDA-approved treatment for reducing the tissue stores of lead.

Wilson's Disease Contributes to the Burden of Heavy Metal Poisoning

Wilson's disease is a less common inborn error of copper metabolism inwhich the endogenous copper carrier protein, ceruloplasmin is decreasedor absent. The result is elevated levels of tissue copper, which isresponsible for the diseases neurological and hepatic complications.Effective therapy exists; however, it is associated with moderate tosevere adverse effects that, in turn, limits its use.

One additional treatment for Wilson's disease is the use of zinc acetate(Galzin). It acts on the intestinal epithelium to prevent the absorptionof copper from dietary sources, which is believed due to the zinc ion byincreasing the production of metallothionein in the enterocyte. Zincacetate is administered orally in the form of gelatin capsules though itshould be separated from food and beverages by at least one hour,preferably on an empty stomach. Twenty-five to 50 mg should be takenthree times per day in adults and strict adherence to the zinc regimenis essential for optimal control of copper distribution. Zinc acetate isindicated for the maintenance of patients with Wilson's disease who havebeen initially treated with a chelating agent and is specifically notrecommended for the initial therapy of symptomatic patients because ofthe delay required for zinc-induced increase in enterocyticmetallothionein and blockade of copper uptake. Source: Galzin (zincacetate) package insert.

As taught by Scheinberg (Scheinberg I H “Wilson's Disease” in Harrison'sPrinciples of Internal Medicine, 12^(th) ed., Wilson J D, et al., eds,pp. 1843-1845) the prevalence of Wilson's disease is approximately1/30,000 or approximately 8700 individuals in the US with this disease.Clinical manifestations of copper excess are rare before age 6 and halfof untreated patients remain asymptomatic through adolescence. Livermanifestations of Wilson's disease may include acute hepatitis,fulminant hepatitis, chronic active hepatitis or cirrhosis. The onlymanifestation may be cirrhosis, which develops insidiously over decades.Neurological or psychiatric disturbances may be the initial presentingmanifestation.

The drug of choice is penicillamine and should be started uponconfirmation of the diagnosis and is administered in divided doses inconjunction with pyridoxine. Additional information about the toxicityof penicillamine may be found above. It usually appears in the first 2weeks and may cause a rash, fever, leukopenia, thrombocytopenia,lymphadenopathy and/or proteinuria. Penicillamine must be discontinuedif these adverse events supervene. Readministration with prednisone canbe successful. Lifelong and continual treatment is required andnon-compliance can be fatal. Successful treatment suggests thatcontinued copper-lowering therapy could prevent virtually everymanifestation of Wilson's disease. Second-line therapy such as trientineis available for patients unable to tolerate penicillamine.

Trientine hydrochloride (Syprine Capsules, bisaminomethylethanediaminedihydrochloride; CAS [112-24-3]) is a white to pale yellow crystallinepowder, which is freely soluble in water. The mechanism appears to beincrease cupriuresis though on a molar basis appears to be lesseffective than penicillamine. Trientine should be administered on anempty stomach at least one hour from ingestion of other drugs, food ormilk. There have been reports of asthma, bronchitis and dermatitisfollowing environmental exposure to inhaled trientine. In addition,systemic lupus erythematosus, dystonia muscular spasm and myastheniagravis have been reported in conjunction with trientine use. Othereffects noted in four patients with biliary cirrhosis includedheartburn, epigastric pain, thickening, fissuring and flaking of theskin, hypochromic microcytic anemia, acute gastritis, aphthous ulcers,myalgias, weakness and rhabdomyolysis.

Arsenic Exposure and Arsenic Poisoning Is Becoming More FrequentlyDiagnosed

Arsenic has recently become more widely discussed in the public media interms of its exposure through drinking water. Although EPA limits formunicipal water supplies exist, some feel this level to be excessive. Itappears that the federal government will reduce the current 50 ppb(parts per billion) limit to 10 ppb. In some defined geographic areas,extremely high levels of arsenic are found in certain wells. Chronicexposure to arsenic at elevated levels has been associated with skindiseases and skin cancer. At present, there are no FDA-approvedtreatments for chronic arsenic exposure.

The health effects of arsenic are well known from several sources:epidemiological studies, accidental exposures, animal toxicologicalstudies and occupational and therapeutic exposures. There are also anumber of factors that must be considered when the toxicity spectrum andseverity are reported. These include the form of the arsenic introducedin vivo (inorganic vs. organic, valence, the salt form, the specificorganic moiety), the route of exposure (inhalational, transdermal,enteral or parenteral), the rate at which the exposure took place(minutes, hours, days, weeks, years or decades) and the degree of priorexposure to arsenic.

Adverse health effects of arsenic are legion and are dependent on manyof the factors listed above. Severe hemolysis followed by renal failureand death may complicate acute inhalational exposure to arsine gas(AsH₃). Hemorrhagic gastritis and gastroenteritis accompanied by nausea,vomiting, diarrhea, convulsions and eventually death from circulatorycollapse may occur within 12 to 24 hours of oral ingestion of arsenictrioxide (As₂O₃) in the range of 1 to 3 mg/kg. There are also a numberof neurologic signs and symptoms that may be associated with oralarsenic trioxide exposure at the same level including encephalopathy,headache, lethargy, confusion, hallucination, seizure and coma.Additional findings may include muscular cramps, facial edema,cytopenias, renal insufficiency, pulmonary edema and hemorrhagicbronchitis. Electrocardiographic abnormalities such as a prolonged QTcinterval and T wave changes have been described.

Chronic exposure may occur by the inhalational, oral, or dermal routes.Numerous organ systems are affected causing a wide array of clinicalsigns and symptoms. Long term exposure may affect small blood vessels,which can manifest in several different ways including Raynaud'sphenomenon, acrocyanosis of the toes leading to gangrene and Blackfootdisease requiring amputation. Post-mortem examination of children withcutaneous signs suggesting arsenic exposure revealed marked thickeningof small- and medium-sized arteries specifically in the coronary,cerebral and mesenteric arteries resulting in myocardial infarction in 2or 5 cases. Neurological signs and symptoms are known to accompanysurvivors of poisoning attempts including peripheral neuropathy andencephalopathy. The peripheral neuropathy begins as paresthesias,hyperesthesias and neuralgias that may later develop into frank pain andmuscle weakness. Histopathological evidence of Wallerian degenerationexists, especially in the long-axon neurons. The findings tend to bebilaterally symmetrical. Recovery is slow and often incomplete. Onclinical and electromyographic grounds, the diagnosis of arsenic-inducedpolyneuropathy may be confused with Guillain-Barre syndrome. Workersfrom copper smelters have noted a variety of upper respiratory signs andsymptoms—presumably from chronic inhalation of arsenic-laden vapors anddusts—including rhinitis, laryngitis and bronchitis. Extreme cases haveresulted in perforation of the nasal septum. Exposure in this samecontext may results in a spectrum of gastrointestinal findings includingnausea, vomiting, and diarrhea. Oral exposure may include the samefindings in addition to abdominal pain. Hepatic injury is also known tocorrelate with chronic oral arsenic exposure including swollen andtender livers, elevations of hepatic enzymes, and may reveal portalfibrosis under histopathological examination. Renal effects of arsenicare also known and include proteinuria, elevated creatinine, hematuria,pyuria and glycosuria in patients with sublethal oral exposure.

Although the specific mechanism has been convincingly described, severalputative mechanisms have been proposed for the finding ofarsenic-induced anemia, leukopenia and the myelodysplastic syndrome.Arsenic may be goiterogenic and diabetogenic. Skin effects of arsenicare well known and include both benign and malignant conditionsincluding hyperpigmentation interspersed with small areas ofhypopigmentation (the so-called “raindrop”-like appearance) distributedon the neck, chest and back; palmar-plantar hyperkeratosis with thecharacteristic small corn-like elevations observed in subjects exposedto arsenic through drinking water. Continued exposure may result inulcerative lesions after several decades. Basal cell carcinoma,epidermoid carcinomas, intraepidermal carcinomas and Bowen's diseaseassociated with arsenic exposure are well described in the medical andepidemiological literature. Cancers of other organs have been reportedto be found in patients living in near proximity to copper smeltersincluding kidney and bladder, in patients having received Fowler'ssolution (potassium arsenate) including lung cancer and in patientsexposed to high arsenic levels in their drinking water in Taiwanincluding bladder, kidney, liver, lung and colon cancer.

SUMMARY

The invention relates to a method of for treating, preventing, andpalliating elevated human blood lead levels, comprising administering toa human in need thereof a pharmaceutical formulation comprising asynthetic sodium aluminosilicate and a pharmaceutically acceptableadjuvant, wherein: (a) the synthetic sodium aluminosilicate isparticulate and at least 90% of the particles are of particle size fromabout 90 μm to about 150 μm; (b) the formulation is administered indoses of about 10 mg to about 1000 mg sodium aluminosilicate.

The invention also relates to a method of treating, preventing, andpalliating elevated human blood ammonia levels, comprising administeringto a human in need thereof a pharmaceutical formulation comprising asynthetic sodium aluminosilicate and a pharmaceutically acceptableadjuvant, wherein: (a) the synthetic sodium aluminosilicate isparticulate and at least 90% of the particles are of particle size fromabout 90 μm to about 150 μm; (b) the formulation is from about 50% (w/w)to about 95% (w/w) water; and (c) the formulation is administered indoses of 2 g to 15 g sodium aluminosilicate.

The invention also relates to a method including administering to ahuman in need thereof a pharmaceutical formulation comprising asynthetic sodium aluminosilicate and a pharmaceutically acceptableadjuvant, wherein: (a) the synthetic sodium aluminosilicate isparticulate and at least 95% of the particles are of particle size fromabout 90 μm to about 150 μm; (b) the formulation is administered indoses of about 5 g to about 12 g sodium aluminosilicate; and (c) thehuman has a higher than normal risk of elevated blood levels of a toxicmetal or has a higher than normal risk of hepatic encephalopathy.

The invention relates to a pharmaceutical formulation, comprising: (a) aparticulate synthetic sodium aluminosilicate wherein at least 90% of theparticles are of particle size from about 90 μm to about 150 μm, (b)about 50% to about 80% by weight water; and (b) a microbialpreservative; and (c) a pharmaceutically acceptable adjuvant; whereinthe formulation contains about 100 mg to about 10,000 mg by weight ofsodium aluminosilicate.

The invention also relates to methods and formulations identical tothose described above, but targeting elevated levels of other toxins, inparticular copper or arsenic. Thus the invention relates to treatment,prevention, and palliation in humans or animals of excess levels oflead, ammonia, copper, and arsenic, as well as other toxins.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a chart showing particle size distribution for a zeolite.

FIG. 2 is a chart showing the relationship between zeolite particle sizeand ammonium absorption using a zeolite.

FIG. 3 is an analysis of the effect of zeolite particle size on ammoniumabsorption.

DETAILED DESCRIPTION

This invention relates specifically to a microporous or mesoporoussilicate, also known as a molecular sieve, which is granular or powderedand which is administered orally, topically or rectally to humans once,daily for several days, weeks, months or years, or more than once dailyfor days to years for the purpose of treating human diseases. Thezeolitic substance is administered in the form or a tablet, capsule orpharmaceutical suspension.

Synthetic zeolites are preferred. As used herein, “synthetic zeolite”means a zeolite manufactured or synthesized by one or more chemicalreactions involving breaking and/or making chemical bonds. “(w/w)” meanspercent by weight, as calculated based on the weight of the componentand the total weight of the composition or formulation. Generally, theterms used in this application are well known to persons of skill in theart.

The granules or powder particles are small enough that diffusion of avariety of ions or other organic or inorganic toxins may freely pass inand through the rigid and well-ordered crystalline structure. It isunderstood that water may or may not comprise the zeolitic materialinitially, but in an aqueous environment such as the human digestivetract, water will virtually completely fill the framework structure.Based on the specific details of the framework structure, it has beenshown that there is a specificity of binding of ions, toxins and otherclasses of molecules.

In one embodiment, a gelatin capsule of the zeolite is swallowed by aperson with a glass of water. In the acidic environment of the stomach,the gelatin capsule dissolve thereby releasing several hundredmilligrams of the zeolite. The zeolite absorbs water to full saturationand forms a slurry. Aluminosilicates are known to be resistant to acidicdegradation at room temperature or body temperatures and therefore theframework structure remains intact during passage through the stomachand is not susceptible to the actions of oral cavity-, stomach- orpancreas-, small bowel- and large-bowel-derived digestive enzymes andperistaltic movements. In the intestinal juices found in the stomach,duodenum, jejunum, ileum and colon poisonous ions and toxins will bindto the zeolite. These poisons or toxins include heavy metals such aslead, copper, potassium, ammonia, mercaptans and hydrogen sulfide.Additional toxins include those that are plant-, marine organism- andnuclear-derived. When a poisonous ion or molecule binds to the zeolite,it is prevented from exerting its toxic effects on the intestinal liningor from being absorbed into the bloodstream for systemic deposition. Animportant feature is that zeolites administered as described may beemployed to remove toxic ions or molecules over the period ofadministration of hours, days, weeks, months or years. The purpose ofthe zeolite is not only intended to prevent the deposition of toxiceffects of a heavy metal or toxin that may be a contaminant of ingestedfood, but additionally it is envisioned to be used in the emergencytreatment of toxic ingestions, radioactive fallout (strontium andcesium), toxic marine organism ingestions, poisoned food ingestions,etc. The zeolite, which binds the adsorbed toxic ions or poisonoussubstances while coursing through the gastrointestinal tract, iseliminated from the body in the feces. An important consideration ishaving the correct surface area to weight ratio for optimal absorptionand minimal toxicity. If the zeolite is powdered too finely, it couldaccumulate in undesirable anatomical locations such as the appendix or adivertuculum, resulting in a pathologic condition. If the zeolite is toolarge, the absorptive capacity as a function of weight decreasessignificantly and substantially larger amounts of the zeolite must beingested to achieve the same amount of absorption.

The particle size distributions cited in this patent are derived from atechnique known as analytical sieving. A full description may be foundin the United States Pharmacopeia, 24^(th) edition (USP 24/NF 19)physical test number <786> as described on pp. 1969-1970, Method 1,which was followed to determine the particle size distribution of theCR-100 sodium aluminosilicate. The following table is illustrative.TABLE 1 Recommended Sieve Size (μm) U.S. Sieve No. ASTM E-11* USPSieves** 4000 5 X X 3350 6 X 2800 7 X X 2360 8 X 2000 10 X X 1700 12 X1400 14 X X 1180 16 X 1000 18 X X 850 20 X 710 25 X X 600 30 X 500 35 XX 425 40 X 355 45 X X 300 50 X 250 60 X X 212 70 X 180 80 X X 150 100 X125 120 X X 106 140 X 90 170 X X 75 200 X 63 230 X X 53 270 X 45 325 X XSource: United States Pharmacopeia, 24^(th) edition (USP 24/NF 19),United States Pharmacopeial Convention, Inc., Rockville, MD; Method<786>, pp. 1969-1970.*American Society for Testing and Materials (ASTM) Specification E-11,U.S. Standard Sieve Series. Additional information may be found to ASTMprocedure STP 447, “A Manual on Test Sieving Methods,” available fromthe ASTM, 100 Bar Harbor Drive, West Conshohocken, PA 19428-2959**The equivalent ISO Standard sieves may be substituted.

The present invention relates to the use of zeolite molecular sieves tobind, sequester and eliminate heavy metals, potassium, ammonia andmercaptans, plant-, marine organism- and fungus/mushroom-derived toxins,radioactive fallout contaminants and hydrogen sulfide and hydrogensulfide-related, endogenously produced chemicals from a human that maybe the source of toxic effects.

For treating, preventing, and palliating high blood lead levels,preferably at least 95% of the particles are of particle size from 90 μmto 150 μm. The formulation may include from about 60% to about 95% byweight water. Preferably, the formulation is a capsule or tabletadministered orally. The treatment is suitable for a human sufferingfrom chronic lead poisoning. The human may have a blood lead level of atleast about 10 μg/dL, at least about 20 μg/dL, at least about 30 μg/dL,at least about 40 μg/dL, or even of at least about 50 μg/dL. The humanmay be between about 2 and about 15 years of age, or may be under about6 years of age. Dosages may be, e.g., about 10 mg to about 1000 mgsodium aluminosilicate, or about 100 mg to about 900 mg, or about 200 mgto about 800 mg. Preferably, the formulation further comprises anantimicrobial preservative or bacteriostat.

The present invention is preferably directed to patients with blood leadlevels of <10.0 μg/dL, 10.0-14.9 μg/dL, 15.0-19.9 μg/dL, 20.0-44.9μg/dL, 45.0-59.9 μg/dL, or >60.0 μg/dL, in each case in combination withone or more therapies recommended for use in the range by state orfederal programs, as exemplified in the State of Minnesota Department ofHealth's Childhood Blood Lead Clinical Treatment Guidelines, March 2001.

For treating preventing, and palliating high human blood ammonia levels,preferably at least 95% of the particles are of particle size from 90 μmto 150 μm. The human may be suffering from hepatic encephalopathy orcirrhosis of the liver. The human may have a history of liver failure.Preferably the formulation is a liquid gel administered orally. Thehuman may have an elevated blood ammonia level or may be at risk forsuch an elevated level. The human may be a hospital in-patient.

While certain particle size ranges are preferred, this is not meant tolimit the scope of the invention. For example, in certain circumstancesvery fine particles of <44 μm may be preferred.

The term “elevated” blood lead level means a level of lead in the bloodthat is above normal, where normal is the specified laboratory's normalrange as determined on blood from non-diseased, healthy volunteers inthe local area, using the local technique-of-choice for the laboratoryperforming the assay (which could include conventional atomic absorptionspectroscopy, graphite furnace atomic absorption spectroscopy, andanodic stripping voltametry) and processed according to the laboratory'sprocedure precisely specifying the type of collection container to use,specifying whether it should be placed immediately on ice, the timeframein which it is to be delivered to the laboratory, and the use of aspecified preservative, if any. A term frequently employed for the upperend of the normal range is the institutional upper limit of normal(IULN), and is intended to have the same meaning as normal for use inthis patent. (Lewandrowski, pp. 820-821.)

By “hyerammonemia” or other terms used to indicate higher than normallevels of ammonia is meant higher levels than normal, where normal isthe specified laboratory's normal range as determined on blood fromnon-diseased, healthy volunteers in the local area, using the localtechnique-of-choice for that laboratory that performed the assay (whichcould be venous blood, arterial blood, or some fraction of whole bloodincluding plasma or serum) and processed according to the laboratory'sprocedure specifying whether it should be placed immediately on ice, thetimeframe in which it is to be delivered to the laboratory, using thespecified preservative, if any. A term frequently employed for the upperend of the normal range is the institutional upper limit of normal(IULN), and is intended to have the same meaning as normal for use inthis patent. (Lewandrowski, pp. 733-735.)

These definitions avoid the controversial nature of clinical laboratoryassay performance which remains unsettled for many reasons includingthat assay principles vary; assay sites differ (hospital laboratoryversus point-of-care versus physician office laboratory versus hometesting); specific reagents vary including proprietary reagents forcommercially available assays; arterial or venous blood may offeradvantages or be specified by method; whole blood versus specificfraction such as plasma, serum or erythrocyte; specific collectioncontainer that has been processed in a specified manner; requirementsexist for the specific assay for preservatives, special handling,temperature, and others; analytical instrument on which assay isperformed may vary; varying normal ranges for assay depending ongeographical location; evolution of actual assay method based on thesame principle. Source: Lewandrowski K., ed. Clinical Chemistry:Laboratory Management and Clinical Correlations, Lippincott Williams &Wilkins, 2002.

For treating, preventing, and palliating high human blood levels ofcopper or arsenic, the same methods and formulations may be used. Thusthe invention relates to treatment, prevention, and palliation in humansor animals of excess levels of lead, ammonia, copper, and arsenic, aswell as other toxins.

“Prevention” means actions, which usually emanate from the workerswithin the health sector that deals with individuals and populationsidentified as exhibiting identifiable risk factors for disease that mayoften be associated with different risk behaviors. Prevention alsorefers to measures not only to mitigate against the occurrence ofdisease, such as risk factor reduction, but also to arrest its progressand reduce its consequences once established. The use of the termprevention in this patent includes the following: primary prevention(which are actions directed towards preventing the initial occurrence ofa disorder); secondary prevention (which are actions that seek to arrestor retard existing disease and its effects through early detection andappropriate treatment); and tertiary prevention (which are actionsintended to reduce the occurrence of relapses and the establishment ofchronic conditions through, for example, effective rehabilitation).

“Palliation” means any form of medical care or treatment thatconcentrates on reducing the severity of the symptoms of a disease orslows its progress rather than providing a cure. It aims at improvingquality of life, and particularly at reducing or eliminating pain. Thedefinition specifically focuses on the general unavailability of a curein that it emphasizes the active total care of patients whose disease isnot responsive to curative treatment. However, in some cases, palliationmay involve alleviation of the side effects of curative treatments, suchas relieving the nausea associated with chemotherapy. The termpalliation is not intended for use in this patent to refer to a chronicdisease, such as diabetes which, although technically incurable, hasavailable treatments that are (ideally) effective enough that it is notconsidered a progressive or life-threatening disease in the same senseas resistant or refractory cancer.

“Treatment” refers to the coordinated healthcare interventions andcommunications for individuals and populations with disease conditionsin which patient self-care efforts are significant. The definition oftreatment in this patent additionally refers to the identification ofone or more disease processes, use or modified use of evidence-basedpractice guidelines (when they exist), collaboration of physicians andsupportive-service providers, patient self-management education, outcomemeasurement, and communication with the patient and other relevantproviders about the outcome of the disease stemming from theinterventions applied.

The present invention may also be used for the treatment of arsenictoxicity derived from arsenic trioxide therapy use in the treatment ofacute promyelocytic leukemia (APL). Although arsenic trioxide has beendemonstrated to be effective in the treatment of relapsed APL (one formof acute myelogenous leukemia), cardiac conduction side effects occurwhich appear to be related to the cumulative dose of arsenicadministered and are exacerbated by other electrolyte abnormalities,such as hypokalemia and hypomagnesemia. If the electrolyte abnormalitiesare corrected and the patient continues to experienced a prolonged QTc(corrected QT) interval or abnormal heart rhythms or associated rapidand irregular heartbeats develop, the manufacturer recommended that thedrug be temporarily discontinued until the QTc interval regresses to<460 milliseconds. Source: Trisenox (arsenic trioxide) package insert,March 2001 revision. Because of sodium aluminosilicates' ability toselective bind metal and metalloid ions, such zeolites assist in thetreatment of arsenic toxicity in the treatment of APL. The presentinvention provides a formulation comprising a synthetic aluminosilicateand arsenic trioxide with a pharmaceutically acceptable adjuvant, and amethod for treating APL by administering a synthetic aluminosilicatetogether with arsenic trioxide whether formulated together orseparately. In this setting, both acute and subacute treatment with 1-10grams orally administered once to multiple times per day is envisioned.However, chronic therapy in the range of 100-1000 milligrams once toseveral times per day is possible.

Recently, arsenic trioxide, administered intravenously, has become theFDA-approved standard of care for relapsed acute promyelocytic leukemia(APL) following therapy with all trans retinoic acid. Followingconventional antineoplastic pharmaceutical development, it is likelythat arsenic trioxide use will become more common and be used earlier inthe management of APL. Patients may achieve a complete remission oftheir disease, leaving them susceptible to the health effects describedabove. At present, there is no described antidote for these effectsbeyond careful monitoring and cessation of the therapy whencomplications outweigh the benefit from continued treatment.

Potassium regenerated sodium aluminosilicate is an alternative fortreatment of hepatic encephalopathy. An important principle in theclinical management of hepatic encephalopathy is treatment of theprecipitating or underlying cause of the encephalopathic episode. Thatis, while a patient may have the established diagnosis of liver failure,only when his or her mental capacity declines is the diagnosis of HEfirmly established. However, often other dietary, pharmacological,electrolyte or infectious influences alter the balance between normalmentation and encephalopathy. Many times, however, the exacerbatingfactor is not determined. While the treatment of HE remains similar tothat described elsewhere in this specification, specific attention tothe precipitating factor (such as a large dietary load of protein,underlying infection, unexpected reaction from an ingested drug oroveruse of certain drugs leading to urinary loss of potassium) iswarranted by the treating physician. Because the use of thepotassium-depleting drugs (namely spironolactone and members of the sameand different classes) is common in patients with liver failure, theycan lead to total body loss of potassium and thereby precipitate anencephalopathic episode. The potassium form of sodium aluminosilicatemay be used instead of the sodium form to treat patients with hepaticencephalopathy. In the manufacturing process, potassium may be exchangedfor sodium in the regeneration process.

The synthetic aluminosilicate is preferably charged with sodium.Alternatively, the synthetic aluminosilicate may be charged with anotheralkali metal, e.g., Li, K, or Rb. The synthetic aluminosilicate mayalternatively be charged with an alkali earth metals, e.g., Ca or Mg.The synthetic aluminosilicate may be chemically modified by methodsincluding pegylation, silation, and glycosylation. The formulation maycontain different particle size distributions of the zeolite ofinterest, and may comprise mixtures of one or more synthetic zeolites.The formulation may contain varying amounts of water, e.g., from about40% or 50% (w/w) up to about 70%, 80%, or 95%(w/w).

The present invention may be used in diagnostic procedures, e.g., todetermine the degree of metal poisoning, as a carrier for x-ray contrastagents, gadolinium based magnetic resonance imaging contrast agents andpositron-emitting metabolites for use in positron emission tomography.The present invention may also be used to control diarrhea, especiallyin conjunction with lactulose in the treatment of hepaticencephalopathy. The present invention may be used in the prevention,treatment, and palliation of Alzheimer's disease, specifically throughthe binding of gut-derived ammonia and preventing its uptake into thesystemic circulation and conferring its toxicity on the central nervoussystem over the course of many years.

A formulation containing the zeolite may also contain an antimicrobialpreservative. The following Table lists examples of antimicrobialpreservatives suitable for formulations of zeolites intended for oral,gastric, enteral or rectal administration. TABLE 2 AntimicrobialPreservative Further Specification Reference benzalkonium chloride pp.27-29 benzoic acid pp. 32-34 benzyl alcohol pp. 35-37 bronopol pp. 40-42butylparaben pp. 49-51 chlorhexidine as various salts pp. 106-110chlorobutanol pp. 111-113 chlorocresol pp. 114-116 cresol includesortho-, meta- pp. 139-140 and para- isomers ethanol pp. 7-9 ethylparabenpp. 191-193 imidurea includes monohydrate pp. 238-239 methylparaben pp.310-313 phenol pp. 336-337 propionic acid as various salts pp. 459-461propylparaben pp. 411-414 sodium benzoate pp. 433-435 sorbic acid pp.470-472 triacetin pp. 534-535Source: Wade A and Weller P J. Handbook of Pharmaceutical Excipients, 2ded., American Pharmaceutical Association, Washington, DC; 1994

The table below exemplifies microorganisms that require reduction oreradication in a zeolite formulation intended for oral, gastric, enteralor rectal administration. These include bacteria and fungi which areknown to be more or less commonly pathogenic and are found in patientssuffering from infections. It is therefore desirable to render thezeolite and associated pharmaceutical adjuvants sterile or with anacceptable low microorganism dose such that patients are not harmed. Thelist includes bacteria (gram positive, gram negative, anaerobic,aerobic, and others), fungi and spores in applicable species. TABLE 3Microorganisms Aeromonas aeorgenes Proteus vulgaris Aspergillus nigerPseudomonas aeruginosa Aspergillus oryzae Pseudomonas cepacia Bacilluscereus Pseudomonas fluorescens Bacillus subtilis Pseudomonas stutzeriCandida albicans Rhizopus nigricans Clostridium histolyticumSaccharomyces cerevisiae Clostridium oedematiens Salmonella enteritidisClostridum sporogenes Salmonella gallinarum Clostridium tetaniiSalmonella paratyphi Clostridium welchii Salmonella typhosaCoynebacterium species Sarcina lutea Enterobacter cloacae Serratiamarcescens Escherechia coli Shigella dysenteriae Klebsiella pneumoniaeStaphylococcus aureus Microsporum species Staphylococcus epidermidisPenicillium chrysogenum Streptococcus faecalis Penicillium digitatumStreptococcus pyrogenes Penicillium notatum Trichoderma lignorumPenicullium roqueforti Trichoderma mentagrophytes Pityrosporum ovaleTrichophyton mentagrophytes Proteus mirabilis Vibrio choleraeZeolites Offer an Unexploited Family of Substances to Remedy HepaticEncephaolpathy and Heavy Metal Poisoning

Nagan (U.S. Pat. No. 6,190,561) discloses a method of water treatmentusing zeolite crystalloid coagulants which is prepared by admixingaqueous sodium silicate and sodium aluminate solutions to form areaction mixture and allowing a reaction to proceed for a sufficienttime to form a zeolite crystalloid coagulant particles with sizes of atleast 4 nanometers before the reaction is terminated. Demmel andVierheilig (U.S. Pat. No. 6,103,949) disclose a family of alkalinephosphate-activated clay/zeolite catalysts, which can be prepared by aprocess wherein a composition of zeolite-clay-phosphate is brought to apH level of about 7.0 to about 14.0. The resulting slurry is then agereacted for ½ to 24 hours and finally dried to produce particles thatare particularly characterized by their high levels of zeolite stabilityfor utilization in the catalytic cracking of petroleum-based materials.Levy (U.S. Pat. No. 5,612,522) describes the use of a zeolite gel toimprove the quality and carbonation of water by the removal of dissolvedgases and minerals. Features not disclosed in these patents include anyapplication to the removal of heavy metals, ammonia, mercaptans andother plant-, marine organism- and nuclear-derived toxins and no use inhumans or animals is discussed.

As taught by Adams, et al. (U.S. Pat. No. 5,560,829), aluminosilicatesof the zeolite P type may be used as calcium binders in aqueoussolutions at low temperatures. Rushmere and Moffett (U.S. Pat. Nos.5,470,435; 5,482,693; 5,543,014 and 5,503,820) describe the preparationof low concentration water soluble polyaluminosilicate microgels, whichare used in the papermaking industry. Neither disclosure discusses anypharmaceutical or therapeutic use or additional utility in the removalof heavy metals, ammonia, mercaptans and other plant-, marine organism-and nuclear-derived toxins from living animals.

Miller and Bruenger (U.S. Pat. No. 5,494,935) discuss the use oflipophilic polyaminocarboxylic acids for the use of heavy metalchelation by oral application. These drugs can be targeted to variousorgans by modification of the length of the alkyl side chain.Undiscussed in their disclosure is the utility of insoluble, finelypowdered substances which can tightly bind heavy metals, ammonia,mercaptans and other plant-, marine organism- and nuclear-derived toxinsexisting in gastric or intestinal juices inside these substances'interstitial crystalline cavities and channels. The method of excretionis unaddressed.

Hu, et al. (U.S. Pat. No. 5,487,882) disclose a method of producingcrystalline synthetic faujasite of the zeolite “X” type. There is nodisclosure of any medicinal, medical, or pharmaceutical uses or anyapplication in the field of heavy metal binding, sequestering or removalfrom living organisms.

Leeper (U.S. Pat. No. 5,478,604) discloses a composition and method forpreventing lead intoxication by the use of a coating which containspolyethylene imine, a calcium compound and/or a silicate that is appliedto a surface which carries a coating of a lead based paint. The objectof this invention is to reduce the digestion and absorption of lead fromthe intestinal tract in case the lead based paint is accidentallyingested. Specific features not found in this prior art is the use fortreatment (as opposed to prevention) of lead poisoning, utility forheavy metals other than lead, months to years of administration,reduction of the total body burden of lead and other heavy metals, anddeliberate oral administration in the form of a capsule or tablet allwith the goal of reversing—partially or completely—adverse effects inheavy metal poisoned mammals. Additional utility for the removal ofammonia, mercaptans and other plant-, marine organism- andnuclear-derived toxins is not discussed.

Perman and Schegel (U.S. Pat. No. 5,320,773) disclose a composition andmethod for purifying water in the form of a tablet containing betoniteclay, attapulgite clay, polymeric coagulant and/or flocculent, biocide,zeolite and activated charcoal. The composition is added to contaminatedwater and removes turbidity, metal and organic contaminants. It isintended for personal use so that safe drinking water can be obtained bythe simple addition of the composition to non-potable water. Schwarz,Putyera, Jagiello and Bandosz (U.S. Pat. No. 5,385,876) disclose aprocess and utility for molecularly engineered activated carbons whichintercalates with a natural or synthetic clay producing a highlymicroporous absorbent material. An organic polymeric precursor iscontacted therewith to fill the matrix interstices. The precursor ispolymerized and carbonized to yield the absorbent material in which thecarbon is intercalated into the mineral matrix. The material consistsessentially of microporous sheets of active carbon spaced from oneanother to define slit-like micropores of a substantially uniformpreselected width that is molecularly engineered such that intersticesbetween the sheets correspond to a given target adsorbate. Only medicaltreatments such as “selective scavengers of ingested poisons” ismentioned as a potential medical use and is too general and non-specificto grasp the specific ideas the inventors had conceived of. Features notdisclosed in these inventions include the use of the aforementionedcompositions for biomedical use including the treatment of specificallyheavy metal poisoning by oral administration of one or more capsules'worth of material daily for months to years intended, or an a more acutebasis with administration into the stomach via nasogastric tube for theremediation of the effects of heavy metals, ammonia, mercaptans andother plant-, marine organism- and nuclear-derived toxins and theirremovable from the human body.

Rainer (U.S. Pat. No. 5,096,946) describes a polymer product for theselective absorption of dissolved ions, which is a water-swellablepolymer which may be physically bound to an open celled cellulosicsponge and which is produced by a thermal process, which inducesamide-forming insolubilization of polyethyleneimine. It has a highaffinity for transition metal ions and may comprise a portion of acellulosic sponge that is permeable to water yet remains substantiallyunaffected by water-borne suspended matter. The patent describes noutility as a pharmaceutical product intended for use as anorally-administered drug in humans or animals. The number of metals thatit has utility in removing further limits it. Yet another limitation isthe absence of any description of other non-transition metal toxicsubstances that it binds such as drugs, organic toxins, heavy metals andtoxic moieties of plant and animal material accidentally ingested.

Withiam (U.S. Pat. No. 5,085,705) discloses a method of preparation andnumerous compositions of alumina-silica-sulfates wherein the sulfate ispresent as a bound network. The compositions include articles ofmanufacture in the form of catalysts, rubber, plastics, paint and paper.Specifically, hollow microspheres containing a porous network are formedby spray drying a gelled composition followed by calcining of thespray-dried hollow microspheres to eliminate the sulfate network.

Dodwell and Smith (U.S. Pat. No. 5,053,139) describe a process for theremoval of heavy metals from aqueous systems containing competing ionsutilizing amorphous tin and titanium silicates. The basic principle ofcation exchange, which is a property of certain specific tin- andtitanium-based molecular sieve zeolites, is exploited in the exchange ofseveral heavy metals with calcium and/or magnesium cations. Thisinvention suffers from no discussion about pharmaceutical applicationsor biomedical uses and does not discuss any utility in removal of toxinsfrom the bodies of animals or humans. Furthermore, the tin- andtitanium-based molecular sieves discussed have an amorphous structurediffering substantially from the present invention in which thecrystalline structure is an important feature.

Kuznicki and Thrush (U.S. Pat. No. 4,994,191) disclose a process for theremoval of heavy metals from aqueous solutions through the use of thecrystalline molecular sieve having the X-ray diffraction pattern ofETS-10 or ETAS-10. They provide examples of the lead absorbing utilityof these molecular sieves showing how the rate of lead binding increaseswith the framework type used. Important features of the presentinvention that are missing from this cited prior art is any utility as apharmaceutical product, envisioned for internal ingestion by a human,that it may be utilized to remove lead absorbed in the tissues of ananimal or human or that it may be used to remove other non-metallictoxins found in plant and/or animal materials which are accidentallyingested by humans.

Wason (U.S. Pat. No. 4,812,299) describes a family of novel and uniquesynthetic alkali metal alumino-silicates, also known as SAMS, whichessentially comprises altered kaolin clay platelets with an integral rimor protuberance of essentially amorphous alkali silicate-kaolin reactionproduct. The unique SAMS compositions are structured materials in whichthe structure can be controlled and are useful as functional fillers, astitanium dioxide extenders, as silica extenders or as reinforcing agentsfor paper, paint, rubber, plastics and specialty products. Thisreferences does not even remotely suggest the utility of these materialsfor use in the pharmaceutical industry, as excipients or active productsin the manufacture of medications for human and animal use, as activecomponents in the removal of harmful substances such as heavy metalsand/or animal or plant-borne toxins.

Hinchey (U.S. Pat. No. 4,348,369) discloses the discovery of, synthesisof and some chemical and physical properties of a novel syntheticcrystalline zeolite of the molecular sieve type, designated “LZ-200”,and envisioned to be used as an absorbent with demonstrated ability toabsorb carbon dioxide, water and methanol. There is not the remotestsuggestion of any biomedical uses, therapeutic uses or pharmacologicaluses of this material, especially in the treatment of toxin-based andheavy metal poisoning in humans is not discussed in the disclosure.

Etzel and Anand (U.S. Pat. No. 4,343,706) disclose a method of removingheavy from industrial waste streams by flocculation using a source offerric ions and an alkaline material at a basic pH. Heavy metals arerecovered by acidifying the floc in a narrow pH range, which liberatesthe heavy metals back into solution while leaving the floc particlesintact and thus reusable. The concentrated heavy metals solution mayalso be recycled or disposed of in an acceptable manner. The use of thismethods and material in humans, as pharmaceutical compositions or in anyin vivo biomedical use is not even remotely described and is undesirablefor several reasons including the administration of ferric ions and thebasic pH which is required for this method to work and which isincompatible with administration by several routes into the human body.

Williams and Mays (U.S. Pat. No. 4,213,874) describe the synthesis ofand several physicochemical properties of amorphous sodiumaluminosilicate base exchange materials with ion exchange capacitiesequal or superior to known crystalline base exchangers and which may beused in water softening and detergents. Murrell, et al (U.S. Pat. No.6,004,527) disclose a method for making molecular sieves with largepores and further describe novel molecular sieve compositions. Heller,Conger and Fitting (U.S. Pat. No. 5,994,933) disclose a method fordistributing molecular sieve powder having a median particle size ofless than about 350 microns, a method for maintaining the moisturecontent of the zeolite particles to greater than about 3 percent, and amethod for refining the powder to reduce the size of the agglomeratedclusters. The use of these materials in humans, as pharmaceuticalcompositions or in any in vivo biomedical use is not even remotelydescribed.

MacDougall, et al (U.S. Pat. No. 5,882,625) describe a faujasite-likealuminosilicate, having a non-uniform aluminum distribution, which issynthesized by crystallizing the zeolite from a mixture of alkali metalaluminate and alkali metal silicate wherein the mixture has an alkalimetal oxide ratio of at least 37. This zeolite has utility as a gasseparation absorbent such as separating oxygen from nitrogen in the air.Otterstedt, Sterte and Schoeman (U.S. Pat. No. 5,863,516) describecolloidal suspensions of discrete particles of colloidal zeolite and amethod for preparing such zeolite from clear tetraalkylammoniumstabilized aluminum silicate solutions. The colloidal suspensions arecharacterized by an average particle size of less than 250 nanometersand a particle size distribution, expressed as a geometric standarddeviation, of less than 1.30 nanometer. These zeolite sols exhibitTyndall light scattering and very low rate of sedimentation owing totheir small particle size. There is no suggestion of any biomedical,pharmaceutical or medical toxicology use.

Ueshima, et al (U.S. Pat. Nos. 5,810,920 and 5,769,938) describe amethod for treating fly ash waste containing harmful metals in which thewaste is mixed with a treating agent containing solid acids and/orcement and additionally a caking inhibitor, which is then kneaded withwater where necessary and solidified by curing. Harmful metals,including lead, cadmium, mercury, chromium, copper, nickel and zinc arestabilized in solidified cakes from which they are not released.Reimers, Akers and Lo (U.S. Pat. No. 4,853,208) disclose a method ofbinding wastes in alkaline silicate matrix as a means of detoxifyingwastes containing heavy metals including mercury, zinc, selenium,arsenic, antimony, copper and thallium. The alkaline silicate matrixbinds the aforementioned metals and prevents their leaching out andcontaminating the environment. There is not even a remote suggestionthat the method and components described in this patent is intended foruse in any biomedical, pharmaceutical or medical toxicology context forany of the metals, ammonia, mercaptans and other plant-, marineorganism- and nuclear-derived toxins disclosed or others not mentioned.

Titterton and Summers (U.S. Pat. No. 5,744,404) describe a process andan article for delivering or applying a zeolitic molecular sieve to anodorous surface. The process involves contacting the surface with aporous article, which contains a slurry of a zeolitic molecular sievehaving a SiO₂/Al₂O₃ ratio of at least 18. The slurry also containswater, ethanol, a suspending agent, a preservative and optionally anemollient. The porous article can be woven or non-woven and includeswipes, pads, foams and towelettes. The patent describes a biomedicalapplication in which said method and resultant slurry is used to controlfoot odor. There is not even the remotest suggestion that this inventioncould be used internally or in the remediation of heavy metal poisoningor toxic metal ingestion in humans or animals.

Henriksen (U.S. Pat. No. 6,136,859) discloses a pharmaceuticalformulation for treating liver disorders which is comprised of selenium,beta-carotene or vitamin A, ascorbic acid in its salt or ester form,alpha-tocopherol, methionine and coenzyme Q10 with a pharmaceuticallyacceptable carrier suitable for treating such diseases as primarybiliary cirrhosis, viral hepatitis, steatohepatitis, alcoholic cirrhosisand related hepatic and biliary disorders. What is not appreciated inthis disclosure is that primary biliary cirrhosis is associated with anelevated serum copper level. The underlying reason for this is unknown.This disclosure does not offer the remotest suggestion that ameliorationof certain clinical findings of primary biliary cirrhosis are achievableby reduction of the elevated serum copper level. One method by whichthis may be achieved is by chelation therapy, either intravenously orenterally.

Nilsson and Stendahl (U.S. Pat. No. 5,662,826) describe a process forthe preparation of a coagulating chemical comprising dissolving a solidzeolite in a solution of trivalent metal salt. The composition describedis a coagulant for water purification in the fields of treating sewagewater, in pulp and paper manufacture, in dewatering organic matter, andin concentrating minerals. Kuhm, Salz and Blasey (U.S. Pat. No.5,645,811) describe a process for the production of very fine-particlezeolitic alkali metal aluminum silicates. Following a mixture of alkalimetal silicate and alkali metal aluminate, in the presence of astoichiometrically excessive amount of alkali metal hydroxide a gel isobtained and matured. Freeman, et al (U.S. Pat. No. 5,591,256) describemethods, uses and compositions of high-performance synthetic alkalimetal alumino-silicates which are characterized by low oil absorptionvalues, high total pore volume and increased differential pore volumes.The products are useful as coating pigments for paper, paperboard, paperfillers, paint pigments and as reinforcing pigments for rubber. There isnot even the remotest suggestion of utility in biomedicine,pharmaceuticals, or that the products could be used in the remediationof heavy metal poisoning or toxic metal ingestion in humans or animals.

Li, et al (U.S. Pat. No. 5,584,912) describe a composition, a synthesisof a composition and a method of using the composition for selectivelyadsorptively separating nitrogen from oxygen wherein the composition isa crystalline EMT with a Si/Al ratio less than 2.0 and a microporevolume of at least 0.20 cm³/g and a lithium cation exchange of at least80%. No pharmaceutical, biomedical or human medicinal or therapeutic useis described in this disclosure.

Tissler, et al (U.S. Pat. No. 5,578,195) describe a syntheticcrystalline aluminosilicate of the pentasil type and method for usingthe same as catalysts or catalyst components in petrochemical processesfor the catalytic conversion of hydrocarbons and their derivatives intouseful organic compounds and intermediates. Pryor and Chi (U.S. Pat. No.4,424,144) describe the preparation of binderless 3A zeolite absorbents,in the form of beads or extrudates and are envisioned for use in dryinga mixture of a hydrocarbon, such as ethylene, and water. Nopharmaceutical, biomedical or human medicinal or therapeutic use isdescribed in this disclosure.

Kuhrts (U.S. Pat. No. 5,641,511) discloses a granular drug deliverysystem comprising a gel-forming dietary fiber that can be made into anorally-ingestible dispersion by admixture with a liquid that can deliveran effective dose of a pharmaceutically-active compound. Although thissystem appears useful in delivering desired amounts of a drug to thegastrointestinal tract, it is not envisioned for use in removing toxicor deleterious substances from the gut. Luck and Crabb (U.S. Pat. No.6,074,689) disclose a method and composition for delivering an activeprotein or peptide to the colon comprising an aqueous solution ofpolyethylene glycol (PEG), the active protein or peptide, and an outerenteric coating. The intended use for this method and composition is fortreatment of antibiotic induced Clostridium difficile-induced diarrheawhere the active protein is hyperimmune bovine colostrum immunoglobulin(HBCIg) against the toxin elaborated by Clostridium difficile.

Bleim and Steffier (U.S. Pat. No. 5,500,212) disclose the composition ofand preparation of a crosslinked amine-containing polymer with apolyfunctional amine-reactive compound such that water insolubility isachieved and bile acid sequestering capacity is enhanced overcholestyramine alone. Dhal, Holmes-Farley and Petersen (U.S. Pat. No.6,294,163) disclose polymers containing guanidinium groups as bile acidsequestrants envisioned for use in lowering serum cholesterol levels.Figuly and Matos (U.S. Pat. No. 5,874,522) disclose crosslinkedpolymeric ammonium salts comprised of n-alkylene or alkyl-substitutedn-alkylene groups and hydrocarbylene radicals containing one or morehydroxyl, ether, amino, thioether, keto or silyl groups envisioned foruse in bile acid binding and serum cholesterol lowering. Goto and Meno(U.S. Pat. No. 6,022,533) disclose a pharmaceutical compositioncomprising an anion exchange resin, silicon dioxide, crystallinecellulose and a pharmaceutical carrier. This disclosure relatesprimarily to the finding that formulation of non-crosslinked anionexchange resins, which had been considered impossible without water, isachievable with the use of silicon dioxide and crystalline cellulose.The tablets containing the anion exchange resin are envisioned for usein lowering cholesterol. Howard (U.S. Pat. No. 4,041,153) disclosesmethods and a pharmaceutical preparation for the treatment ofhypercholesterolemia, which contains clofibrate, a basic anion exchangeresin and a metal ion whose function is to form insoluble metal bileacid salts. The ingestible non-toxic metallic compound is capable ofdissolving in the gastrointestinal juices to yield a metallic salt orion that can react with bile acids to form an insoluble or poorlysoluble metal salt of these bile acids. Huval, Holmes-Farley, Petersenand Dhal (U.S. Pat. No. 6,264,938) disclose a combination therapy forhypercholesterolemia, which is comprised of a conventional HMG-CoAreductase inhibitor and an unsubstituted polydiallylamine polymer, whichacts as a bile acid sequestrant. Johnson (U.S. Pat. No. 4,649,048)discloses that quaternized vinylimidazole-ethylene glycoldimethacrylates useful to sequester non-absorbed bile acids in theintestinal tract to form a complex, which is then excreted in the feces.Jaxa-Chamiec, Hickey and Shah (U.S. Pat. Nos. 4,594,339; 5,230,885 and5,273,740) disclose several classes of anion exchange polymersenvisioned for use in treating hypercholesterolemia by binding free bileacids in gastrointestinal juice and sequestering them for eventualexcretion out of the body with the feces. The specific anion exchangepolymers disclosed includeN,N-dimethyl-N-dodecylammoniomethyl-substituted polystyrene,N,N-dimethyl-N-dodecyl-ammoniomethylstyrene-ethylmethacrylate-divinylbenze and6-(N,N-dimethyl-N-octylammonio)hexanoylated polystyrene chloride. Shawand Sharma (U.S. Pat. No. 4,790,991) disclose ingestible aggregatescomprising a pre-swelled anhydrous hydrocolloid and a substrate and areenvisioned for use in treating a number of diseases includinghypercholesterolemia and mineral deficiencies, in combination with theappropriate active pharmaceutical ingredient. Yang, Sharma, Sheu andShaw (U.S. Pat. No. 4,778,676) disclose a chewable confectionerydelivery system for active pharmaceutical ingredients and specificallycholestyramine intended for improve palatability in the treatment ofhypercholesterolemia with a bile salt binding resin. Schulz (U.S. Pat.No. 5,167,965) discloses the composition of and method of producingpalatable cholestyramine granules and tablets to be used in thetreatment of hypercholesterolemia. These disclosures do not address anyuse in heavy metal poisoning and do not address any compositions such aszeolite molecular sieves.

McClelland and Zentner (U.S. Pat. No. 5,350,584) disclose a process forspheronization of charged resins, which produces multiparticulates 0.3-3mm in diameter and which is microcrystalline free. Active pharmaceuticalagents envisioned for incorporation into a granulation that is thenspheronized include cholestyramine and trientine. Although each activepharmaceutical ingredient is used in specific circumstances, there is nospecific mention of this process or these compositions to be used in thelong-term remediation of heavy metal poisoning and removal of the heavymetal itself, nor is there any discussion about the use of zeolitemolecular sieves.

Porath (U.S. Pat. No. 5,183,313) discloses an absorbent for metal ions,proteins and other inorganic and organic substances which is based upona ligand with an atomic sequence of N—C—C—N where the specific sequencecomprises part of a heteroaromatic ring system which is covalentlybonded to a polymers such as a polysaccharide, polyvinyl alcohol orother organic hydrophilic polymer. The invention suffers from nodescription about any in vivo biomedical use such as may be effected byoral administration of a capsule or tablet. There is a further absenceof any description of this material being employed in a heavy metalchelating mode for other heavy metals, including lead, uranium, andothers, ammonia, mercaptans and other plant-, marine organism- andnuclear-derived toxins.

Hider, Kontoghiorghes and Silver (U.S. Pat. No. 4,585,780) disclose aseries of pharmaceutical compositions containing a 3-hydroxypyrid-2-oneor 3-hydroxypyrid-4-one in which the atom attached to the nitrogen atomis replaced by an aliphatic acyl group, by an aliphatic hydrocarbongroup, or by a substituted aliphatic hydrocarbon group to be used forthe removal of toxic amounts of metals from the body.

These materials differ substantially from the present invention in thatthey are of an organic nature designed to permeate cellular membranes.In addition, the mode of action of these compounds is to enhance thewater solubility and urinary excretion of metals such as iron, copperand aluminum. Yet another important difference from the presentinvention is the solubility of the chelating compound itself and itsproperties of systemic distribution.

Wieder (U.S. Pat. No. 4,352,751) discloses a series of species-linkeddiamine triacetic acids and their metal chelates whose general structureis comprised of an organic species containing at least one amine,hydroxyl or thiol functional group and a two or more atom long covalentbridge. Very different than the present invention, the utility proposedis in the monitoring the level of biologically and/or medicallyimportant molecules. This is achieved by incorporating into the metalbinding sites, rare earth metal ions capable of forming fluorescentchelates that may be used in a fluorometric assay. No therapeutic intentis even remotely suggested in addition to the extremely small capacityto bind toxic metal or other toxins of medical interest for the purposeof their elimination.

Hinckley (U.S. Pat. No. 4,346,216) teaches the use of osmiumcarbohydrate complexes as pharmaceutical compositions for the treatmentof heavy metal poisoning, arthritis and as a diagnostic aid as aradiographic contrast agent. Osmium-glucose complexes are proposed to beadministered to mammals suffering from heavy metal poisoning which willresult in a chelation of the heavy metal within the osmium complex in aharmless form which is then excreted from the system without furthertoxic effects on the treated animal. This approach suffers numerousdisadvantages including the unavoidable and potentially deleteriousdeposition of osmium metal in tissues, unevaluated ability of thematerial to be absorbed from the gastrointestinal tract, and the needfor multiple, frequent, chronic injections and undisclosed method ofelimination from the body of a mammal. The mechanism of action alsovaries significantly from the present invention in that in that onlylead is discussed as one of the heavy metals susceptible to thisapproach. Additionally, osmium is generally regarded as toxic to thehuman body and strict federal limits on the amount of osmium that may bedeposited limits the utility of this approach.

Mandeville and Holmes-Farley (U.S. Pat. No. 5,702,696) disclose a familyof hydrophilic anionic exchange resins for use in treating iron overloadsyndromes by decreasing the absorption of dietary iron. Sasaki and Ishii(U.S. Pat. No. 6,180,094) disclose a medicament, which comprises as anactive ingredient a weakly basic anion exchange resin chelating withferric ion, which adsorbs phosphate ions in vivo and is used forprevention and treatment of hyperphosphatemia. In this disclosure, theiron binding properties of cholestryamine are mentioned and thesuggestion that iron deficiency anemia may be caused by its and othersimilar resins's use. Although there are certain advantages to thisapproach, there is no mention of any use of this method in the removalof heavy metals, ammonia, mercaptans and other plant-, marine organism-and nuclear-derived toxins nor is there mention that zeolite molecularsieves can be employed in the same manner.

Rosenberg (U.S. Pat. No. 4,107,331) describes a zinc chelatingfungicidal composition in which zinc ions—which are required by certainspecies of fungi for growth—is sequestered in the chelating agentthereby preventing growth of human fungal infections. The chelating orsequestering agents described include water soluble salts of one ofseveral EDTA-like organic compounds which is mixed with an aqueous jellyand administered vaginally for the treatment of common yeast infections.This disclosure suffers from a number of disadvantages for the treatmentof chronic heavy metal poisoning including its use as a topicaltreatment and the use of organic and toxic chemicals about which littletoxicity information in man is known. Additionally, oral administrationfor months in the form of a capsule, tablet, suspension or slurry forthe purpose of removing heavy metals, ammonia, mercaptans and otherplant-, marine organism- and nuclear-derived toxins from the body is noteven remotely suggested.

Bergwitz-Larsen and Ulf (U.S. Pat. No. 5,643,560) disclose a drugformulation with ion exchangers of the carrageenan type for use inreducing toxic side effects and lethality when overdosing psychotropicmedications. The drug and the carrageenan are administered together, butthe carrageenan, through the process of ion exchange, in conjunctionwith an additional salt, minimizes absorption as reflected in animalmodel serum levels of clomipramine. This disclosure, however, fails toaddress the use of zeolite molecular sieves in vivo nor does it addressthe issue of chronic toxicity from tissue absorbed heavy metals,ammonia, mercaptans and other plant-, marine organism- andnuclear-derived toxins, nor does it address use ranging from months toyears.

Howes and Newman (U.S. Pat. No. 6,045,834) disclose compositions andmethods for the removal of mycotoxins from animal feed whereby acombination of modified yeast cell wall extract and mineral clay is fedto animals in amounts sufficient to inactivate mycotoxins present in thefeeds. These compositions are intended to be admixed with feeds,incorporated directly into pelleted feeds or fed directly to animals.This invention suffers from several deficiencies for use in thetreatment of heavy metal poisoning or toxic ingestions in man includingpreparation using the cell wall of yeasts which may contain unknownand/or undesirable contaminants or biologically active molecules and nodescription of any kind that said composition may be useful in othertoxins such as heavy metals, ammonia, mercaptans and other plant-,marine organism- and nuclear-derived toxins.

Casas and Mosstam (U.S. Pat. No. 5,837,238) disclose a therapeuticmethod of treating rotavirus induced diarrhea by the administration oflyophilized and reconstituted Lactobacillus reuteni whose mechanism ofaction is unknown although it may be related to the elaboration of asubstance named reuterin or improving the indigenous gastrointestinalmicroflora. Willoughby and Yolken (U.S. Pat. No. 5,192,551) disclose aneutral glycolipid GA1 (asialo-GM1 or asialo-gangliotetraosylceramide)as an adsorbent, either alone or bound to a non-absorbable resin ormatrix, for the neutralization of enteric viral pathogens representingeither prophylaxis in the case of a localized outbreak, or as atreatment in the case of florid gastroenteritis. Delivery modality isdependent on location; pharyngeal colonizing viruses is proposed to beaccomplished by nebulization or gargling whereas gastrointestinalinfection is treated specifically with internally ingested naked GA1 orGA1 bound to beads, resins, natural or synthetic polymers although yetadditional delivery methods and pharmaceutical dosage forms arementioned. This invention does not specifically claim to work bysequestration or ion exchange, it is not directed toward remediation ofany toxic effect produced by heavy metal ingestion and it does notinvolve the use of zeolite molecular sieves.

Several disclosures reveal similar methods of increasing the nutritionalvalue of mycotoxin-contaminated animal feed by feeding the animalmontmorillonite clay [Beggs (U.S. Pat. No. 5,149,549)] or anacid-activated montmorillonite clay [Turk, Music and Beall (U.S. Pat.No. 5,639,492)] simultaneously with the contaminated animal feed. Theclay, itself which is not absorbed in the gastrointestinal tract butwhich absorbs or adsorbs any one of several known toxins (aflatoxin,fumonisin, vomitoxin, ochratoxin, zearalenone, ergot, and ergotamine).Taylor, Delaney and Phillips (U.S. Pat. Nos. 5,165,946 and 5,165,946)disclose a dry solid animal feed composition in which biodegradable feedis contaminated with a mycotoxin and is admixed with a mycotoxininactivating agent comprising particles of a phyllosilicate mineralcapable of inactivating mycotoxins. The particles are coated with asequestering agent in an amount sufficient to enhance the mycotoxininactivating capacity of the phyllosilicate. These inventions sufferfrom several deficiencies including no mention of the use of zeolitemolecular sieves, no mention of the chronicity of administration, nomention of any additional nutritional deficiencies that may result fromthe clay administration and no mention of specificity of toxin bindingwithin the framework structure. Specific pharmaceutical preparation forhuman use is not discussed. Moreover, human use was not described inthese disclosures.

Geneix, Alafourcade and Ribereau-Gayon (U.S. Pat. No. 4,765,992)disclose a method of improving the alcoholic fermentation yield by theaddition of cell walls that have been boiled or autolysed and washed.The cell walls act to bind the offending substances which includecertain fatty acids and their ethyl esters, pesticide residues andsubstances secreted by microorganisms. There is not even the remotestsuggestion that this invention has utility in biomedicine,pharmaceuticals or could be used in the remediation of heavy metalpoisoning or toxic metal ingestion in humans or animals.

Robbins and Seely (U.S. Pat. No. 4,251,519) disclose a process oflowering or preventing an increase in the level of cholesterol andtriglycerides in the blood of mammals by including a yeast glycan in thedaily diet in an amount of up to 30% of the total food intake. There isnot even the remotest suggestion that this invention has utility inbiomedicine, pharmaceuticals or could be used in the remediation ofheavy metal poisoning or toxic metal ingestion in humans or animals.

Coe, Gafffiey, Srinivasan, Kirner, Pierantozzi and White (U.S. Pat. Nos.4,925,460; 5,152,813 and 5,258,058) disclose different methods by whichto achieve improved gas separation including the use of a lithiumexchanged chabazite, a binary exchanged X-zeolite containing lithium,calcium and/or strontium ions, and additional divalent cation exchangedlithium X-zeolites. Maurer (U.S. Pat. No. 5,171,333) discloses a processfor methane purification by pressure swing absorption employing afaujasite type of zeolite containing divalent and alkali metal andalkaline earth metal cations. Fitch, Bulow and Ojo (U.S. Pat. No.5,464,467) disclose type X zeolites with charge compensating cationscomprised of lithium, aluminum, cerium, lanthanum and/or mixedlanthanides are useful in gas separations. Chao, Sherman, Mullhaput andBolinger (U.S. Pat. No. 5,413,625) disclose lithium/alkaline earth metalA and X zeolites are useful in separating oxygen and nitrogen from gasmixtures owing to their high absorptive capacity and high thermalstability. There is not even the remotest suggestion that the object ofany of these inventions has utility in biomedicine, pharmaceuticals orcould be used in the remediation of heavy metal poisoning or toxic metalingestion in humans or animals.

A number of microporous compositions are described in the patentliterature. Vaughan, Barrett, Strohmaier, Treacy and Newsam (U.S. Pat.Nos. 4,091,079; 4,333,859; 4,879,103 and 5,116,590) disclose thesynthesis of several new materials including a synthetic large porecrystalline metalsilicate zeolite composition designated ECR-35, acrystalline aluminosilicate zeolite comprised of potassium and vanadiumions present in the reaction mixture designated VK-2, a high silicafaujasite polymorph designated CSZ-3 which has claimed utility insorption, separation and catalytic applications, and a zeolitecharacterized by triethyl methyl ammonium being entrapped in supercagesof the aluminosilicate and designated ECR-30. Delprato, Guth, Angelrot,Didier and Zivkov (U.S. Pat. No. 5,393,511) disclose the synthesis offaujasite class zeolites in which numerous crown ethers and othercarbon-containing macropolyrings of the polyoxadiazabicycloalkane classare employed as structuring agents. Wilson, Lok and Flanigen (U.S. Pat.No. 4,310,440) disclose a family of crystalline microporousaluminophosphate compositions, designated the AlPO₄ family of zeolites,the members of which are synthesized by hydrothermal crystallization atelevated temperatures of aluminophosphate gels containing a molecularstructure-forming template and which are envisioned for use as catalystsor catalyst bases. Patton and Gajek (U.S. Pat. No. 4,473,663) discloseanother crystalline aluminophosphate, designated AlPO₄-33, although itis distinct from the aforementioned AlPO₄ family described above. Chang,Chu, Dessau, Higgins, Lutner and Schlenker (U.S. Pat. No. 5,091,073)disclose a crystalline molecular sieve composition, designated MCM-37,which may be used in the catalytic conversion of organic compounds.Breck and Acara (U.S. Pat. No. 4,950,952) disclose a crystallinezeolite, designated T, and Breck, Blass, and Skeels (U.S. Pat. No.4,503,023) disclose silicon substituted zeolite compositions which arecontacted with an aqueous solution of a fluorosilicate salt usingcontrolled proportions and temperature and pH conditions which avoidaluminum extraction. Casci, Lowe and Whittam (U.S. Pat. No. 4,537,754)disclose the composition of and the method of producing zeolite EU-1which is useful in catalytic processes such as xylenes isomerization.Grose and Flanigen (U.S. Pat. No. 4,124,686) disclose a crystallinezeolite, designated phi, which is prepared hydrothermally from aqueousgels, exhibits large-pore adsorption characteristics and is envisionedfor use in hydrocarbon conversion processes exemplified by isoparaffinalkylation, hydrocracking isomerization and reforming. Morimoto, Takatsuand Sugimoto (U.S. Pat. No. 4,578,259) disclose a crystallinealuminosilicate and its structural variations, collectively designatedISI-6, which are envisioned for use as catalysts for the conversion ofoxygen-containing organic compounds such as alcohols and ethers intohydrocarbons. Plank, Rosinski and Rubin (U.S. Pat. No. 4,016,245)disclose a crystalline zeolite, designated ZSM-35, which is envisionedfor use as an absorbent or a catalyst. Sand and Dodwell (U.S. Pat. No.4,081,514) disclose a process for producing acid-stable, fluidizablemordenite particles in the size range of 20 to 150 nanometers andenvisioned for use as an absorbant, catalyst support and ion-exchangemedium. Sand (U.S. Pat. No. 4,093,699) independently discloses a methodfor making synthetic offretite, which is acid treated, and is capable ofintercrystalline absorption of benzene and molecules greater than 5 Å.Cormier and Sand (U.S. Pat. No. 4,017,590) disclose the preparation ofsynthetic ferrierite by a hydrothermal process in which there isco-precipitation of silica-alumina gels and sodium and potassiumcarbonates and bicarbonates and which is envisioned for use inseparating molecules 6.2 Å and smaller from larger molecules. Kuznickiand Whyte (U.S. Pat. No. 5,011,667) disclose a process of formingself-bound sodium chabazite and designated EC-20 which shows superiorityin absorption and ion-exchange capacity when compared to the naturalform. Velten and Demmel (U.S. Pat. No. 4,826,793) disclose a method ofincorporating small crystalline catalytic ingredients into anattrition-resistant matrix by the use of binder formulations preparedfrom amorphous silica, alumina, and zirconia. The particles are lessthan 4 μm and contain the catalyst component ZSM-5, low-soda exchangedtype Y-zeolite or ultra-stable type Y zeolite. The resulting material isspray-dried and calcined and which has shown resistance to attrition andparticle density change. In each of these disclosures there is not eventhe remotest suggestion that these inventions have utility inbiomedicine, pharmaceuticals or could be useful in the remediation ofheavy metal poisoning or toxic metal ingestion in humans or animals.

Bacon Kurtz and Fitzpatrick (U.S. Pat. No. 6,270,755) disclose a seriesof anionic polymers as toxin binders intended for use in bindingpathogenic toxins elaborated by microorganisms including bacteria andprotozoa. Kurtz and Fitzpatrick (U.S. Pat. No. 6,290,946) disclose aseries of polystyrene sulfonate-based polymers also intended for use inbinding pathogenic toxins from microorganisms. Fitzpatrick, Huval, BaconKurtz, Mandeville and Neenan (U.S. Pat. Nos. 6,007,803 and 6,290,947)disclose a cationic polymer comprised of a monomer having a pendantammonium group and a hydrophobic monomer envisioned for use in bindingpathogenic toxins elaborated by microorganisms including bacteria andprotozoa. Heerze and Armstrong (U.S. Pat. No. 6,107,282) discloseprevention and/or treatment of antibiotic associated diarrhea andpseudomembranous enterocolitis arising from Clostridium difficile toxinB using 8-methoxycarbonyl oligosaccharides. These compositions bind thetoxin and neutralize it thereby mitigating and potentially preventingthe toxin's pathological effects. Such oligosaccharides have been shownto be eliminated completely and rapidly from the rat gastrointestinaltract. These inventions suffer from no description of any use inremoving heavy metals, ammonia, mercaptans and other plant-, marineorganism- and nuclear-derived toxins either recently ingested orabsorbed into tissue from chronic exposure.

Other forms of heavy metal detoxification are clearly needed for chronicadministration.

The inorganic structural class of molecular sieves or zeolites iscomprised of more than 1000 members, many of which we believe possessuseful medicinal, pharmacological and biopharmaceutical properties inthis therapeutic area.

Zeolites are a class of inorganic crystalline microporous solidscomprised mostly of silicates and phosphates although arsenates andgermanates are also represented. Zeolites possess a framework density(FD) of approximately 12.1 to 20.6 tetrahedrally coordinated atoms (alsoknown as T-atoms) per 1000 Å³(cubic angstroms). Such frameworks arecomprised of a number of repeated identical or different structuralcomponents termed secondary building units (SBU). To date, approximately20 SBUs have been described. The framework for a specific zeolitedefines the pore and channel sizes; these pore and channel diametersvary across different zeolites. The pore and channel diameters, alsotermed “crystallographic free diameters,” influence the rate ofdiffusion of water and dissolved ions through the framework. A number ofzeolite groups with 20-, 18-, 14-, 12-, 10-, 9-, and 8-ring structuresare known to exist. Depending on the relative molecular charge in thespace surrounding the pores positively or negatively charged ions areattracted or repelled. Ions of similar charge and size may besubstituted for each other or “exchanged” thereby producing the “ionexchange” phenomenon for which zeolites are well known.

Zeolites offer a unique approach to treating heavy metal poisoningbecause of their intrinsic chemical and physical stability and theirgeneral biological inertness. The specific zeolite isotypic groupsconsidered to be useful in the wide spectrum of heavy metal intoxicationinclude the 20-, 18- and 14-ring structures designated by the terms andabbreviations: Cloverite (-CLO), VPI-5 (VFI), AlPO-8 (AET), CIT-5 (CFI),UTD-1F (DON), OSB-1 (OSO); the 12-ring structures AlPO-5 (AFI), SAPO-40(AFR), MAPSO-46 (AFS), CoAPO-50 (AFY), ASU-7 (ASV), AlPO-31 (ATO),MAPO-36 (ATS), Beta (BEA), Boggsite (BOG), Beryllophosphate-H (BPH),Cancrinite (CAN), CIT-1 (CON), Chiral Zincophosphate (CZP), DAF-1 (DFO),EMC-2 (EMT), Faujasite (FAU), Gmelinite (GME), GUS-1 (GON), ITQ-4 (IFR),ITQ-7 (ISV), Linde Type L (LTL), Mazzite (MAZ), ZSM-18 (MEI), Mordenite(MOR), ZSM-12 (MTW), Offretite (OFF), UiO-6 (OSI), Roggianite (RON),STA-1 (SAO), UCSB-8Co (SBE), UCSB-6GaCo (SBS), UCSB-10GaZn (SBT), SSZ-48(SFE), VPI-8 (VET); the 10-ring structures AlPO-11 (AEL), AlPO-41 (AFO),AlPO-H2 (AHT), Co-Ga-Phosphate-5 (CGF), Co-Ga-Phosphate-6 (CGS),Dachiardite (DAC), Epistilbite (EPI), EU-1 (EUO), Ferrierite (FER),Heulandite (HEU), Laumontite (LAU), ZSM-11 (MEL), ZSM-5 (MFI), ZSM-57(MFS), ZSM-23 (MTT), MCM-22 (MWW), NU-87 (NES), Partheite (PAR), SSZ-44(SFF), SSZ-35 (STF), Stilbite (STI), Terranovaite (TER), Theta-1 (TON),Weinebenite (WEI), Wenkite (WEN). The specific zeolite isotypic groupsconsidered to be useful in the wide spectrum of heavy metal intoxicationalso include the 9-ring structures designated by the terms andabbreviations: Chiavennite (CHI), Lovdarite (LOV), Natrolite (NAT),RUB-17 (RSN), SSZ-23 (STT), VPT-7 (VSV). The specific zeolite isotypicgroups considered to be useful in the wide spectrum of heavy metalintoxication also include the 8-ring structures designated by the termsand abbreviations: Li-A (ABW), ACP-1 (ACO), AlPO-18 (AEI), AlPO-EN3(AEN), AlPO-14 (AFN), AlPO-52 (AFT), SAPO-56 (AFX), Analcime (ANA),AlPO-C (APC), AlPO-D (APD), MAPO-39 (ATN), AlPO-12-TAMU (ATT), AlPO-25(ATV), AlPO-21 (AWO), AlPO-22 (AWW), Bikitaite (BIK), Brewsterite (BRE),Cesium Aluminosilicate (CAS), Chabazite (CHA), Deca-dodecasil 3R (DDR),DAF-2 (DFT), TMA-E (EAB), Edingtonite (EDI), Erionite (ER1), ERS-7(ESV), Gismondine (GIS), Goosecreekite (GOO), ITQ-3 (ITE), NaJ (JBW),ZK-5 (KFI), Levyne (LEV), Linde Type A (LTA), Merlinoite (MER),Montesommaite (MON), MCM-35 (MTF), Paulingite (PAU), Phillipsite (PHI),Rho (RHO), RUB-3 (RTE), RUB-13 (RTH), STA-6 (SAS), STA-2 (SAT), Mg-STA-7(SAV), Thomsonite (THO), Tschortnerite (TSC), VPI-9 (VNI), Yugawaralite(YUG), ZAPO-MI (ZON). These zeolites are described by Baerlocher andcolleagues (Baerlocher Ch., Meier, W M and D H Olson. Atlas of ZeoliteFramework Types, 5^(th) revised ed., Elsevier, 2001, pp. 3-18).

One related mineral, magnesium aluminum silicate [1327-43-1] also termedaluminum magnesium silicate [12511-31-8] is available commercially as apharmaceutical excipient. It is used in a range concentrations in thepharmaceutical industry and functioning as an absorbent, a bindingagent, a disintegrant, an oral or topical emulsion stabilizer, an oralor topical suspending agent, a stabilizing agent and a viscositymodifier. It is obtained from the silicate ores of the montmorillonitegroup and occurs as an off-white to creamy white, odorless, tasteless,soft, slippery small flakes or as fine micronized powder. It ispractically insoluble in alcohols, water and organic solvents. It canswell to many times its original volume in water and may be dried andrehydrated many times. It is stable indefinitely when stored under dryconditions and is stable over a wide pH range. It absorbs some organicsubstances but appears to be compatible with organic solvents. It isgenerally regarded as nontoxic and nonirritating at levels employed as apharmaceutical excipient. Subacute animal feeding studies in rats anddogs fed magnesium aluminum silicate at 10% of their diet for 90 dayswere negative including autopsy and histopathological examination. Theoral LD₅₀ for the rat is 16 g/kg. Magnesium aluminum silicate isincluded in the Food and Drug Administration's (FDA) InactiveIngredients Guide.

The present invention relates to the use of zeolites, both natural andartificial, in the treatment of diseases related to heavy metals andammonia in humans. Based on the relative affinities and diameters of themetallic ions, certain metals will bind preferentially to certainzeolites, thus creating the ability to design lattice structures ofprecise dimensions for each of the heavy metals that are known poisonsin man. The specific metals known to cause human disease in elevatedquantities include lead, copper, tin, arsenic, antimony, beryllium,bismuth, boron, cadmium, chromium, cobalt, copper, iron, lead, lithium,magnesium, nickel, selenium, silver, strontium, thallium, tin, titanium,vanadium, zinc, mercury. It is envisioned that the zeolite would beadministered orally in the form of a capsule, tablet, powder or slurrydaily or multiple times daily for weeks' to months' duration. Zeolitesare generally insoluble in the aqueous environments present in the humangastrointestinal tract such as acid pH in the stomach, alkaline pH ofthe duodenum for the few hours of normal transit time. Dealuminizationis known to occur in acidic environments with some zeolites. The neutralpH of the jejunum, ileum, cecum, colon and rectum do not pose adealuminization or solubility risk. It is known to bind lead and copperwhen administered orally in an in vivo system.

Although zeolites and similar ion exchange, inorganic, relativelyinsoluble materials are claimed, the specific zeolite to be employed isthe sodium aluminum silicate, CAS [12141-46-7]. As shown in the MaterialSafety Data Sheet (Material Safety Data Sheet for sodium aluminumsilicate, CAS [12141-46-7] manufactured by Mineral-Right, Inc.,Phillipsburg, Kans. Revised Mar. 22, 1995) it consists in its physicalstate as a solid in the form of granular crystals, which arewhite-opaque in color. The specific gravity of sodium aluminum silicateis 0.80. It is insoluble in pH neutral aqueous solution. It is formedfrom two ingredients: hydrated alumina [1344-28-1] 21% and sodiumsilicate [134409-8] 68%. It is known to be non-toxic to ingestion. It issubject to the following environmental protection procedures:conventional housekeeping methods. It is to be handled similar to earth.This material demonstrates temperature-dependent weight loss uponheating which appears to be unchanged in the temperature range betweenapproximately 350° F. and 1200° F. (Research Report Covering HighTemperature Tests on the MR-1 Synthetic Zeolite, Baumbach Labs,Appleton, Wis.; Dec. 30, 1993). At higher temperatures, the “ZeoliteReflection Phenomenon” has been observed.

Examples of zeolites useful in the present invention include zeoliteLi-A (Barrer and White) (Barrer R M, et al., J. Chem. Soc. 1267-1278,1951; Kerr I S, Z. Kristallogr. 139:186-195, 1974; Krogh Anderson E, etal. Z. Kristallogr. 176:67-73, 1986); [Be—As—O]-ABW (Gier T E, et al.Nature 349:508-510, 1991; Harrison W T A, et al., Acta Crystallogr.C51:181-183, 1995); [Be—P—O]-ABW (Gier T E, et al., Nature 349:508-510,1991; Harrison W T A, et al., Acta Crystallogr. C51:181-183, 1995; RoblC, et al. J. Chem. Soc. Dalton Trans. 1911-1912; 1993); [Ga—Si—O]-ABW(Newsam J M, J. Phys. Chem. 92:445-452; 1988); [Zn—As—O]-ABW (Gier T E,et al. Nature 349:508-510; 1991); [Zn—P—O]-ABW (Gier T E, et al. Nature349:508-510; 1991); |Cs—|[Mg—P—O]-ABW (Rakotomahanina Raloisoa E L,Ph.D. Thesis, U. Grenoble; 1972); |Cs—|[Al—Si—O]-ABW (Klaska R, et al.Naturwiss. 60:299, 1973; Klaska R, et al. Z. Kristallogr. 142:225-238,1975); |Cs—|[Al—Ti—O]-ABW (Gatehouse B M, et al. Acta Crystallogr.C45:1674-1677, 1989); |Li—|[Al—Si—O]-ABW (Ghorbarkar H, Cryst. Res.Technol. 27:1071-1075, 1992); |Li—|[Zn—P—O]-ABW (Harrison W T A, et al.J. Solid State Chem. 114:249-257, 1995); |Li—|[Al—Ge—O]-ABW (Tripathi A,et al., Microporous and Mesoporous Materials, 34:273-279, 2000);|Na—|[Co—P—O]-ABW (Chippindale A M, et al., Acta Crystallogr., C55:845-847, 1999); |Rb—|[Co—P—O]-ABW (Rakotomahanina Raloisoa E L, Ph.D.Thesis, U. Grenoble, 1972); |Rb—|[Al—Si—O]-ABW (Klaska R, et al.,Naturwiss., 60: 299, 1973; Klaska R, et al., Z. Kristallogr.142:225-238, 1975); |Tl—|[Al—Si—O]-ABW (Krogh Anderson E, et al.,Zeolites, 11: 149-154, 1991); ACP-1 (Feng P Y, et al., Nature, 388:735-741, 1997); AlPO-18 (Simmen A, et al., Zeolites, 11:654-661, 1991;U.S. Pat. No. 4,310,440, 1982); AlPO-11 (Bennett J M, et al., Zeolites,7: 160-162, 1987; Richardson Jr J W, et al., Acta Crystallogr., B44:367-373, 1988; Wilson S T, et al., U.S. Pat. No. 4,310,440, 1982);MnAPO-1 (Pluth J J, et al., J. Phys. Chem., 92: 2734-2738, 1988);SAPO-11 and compositional variants (Flanigen E M, et al., Pure Appl.Chem., 58: 1351-1358, 1986; Flanigen E M, et al., In Proc. 7^(th) Int.Zeolite Conf., Japan, 103-112, 1986); AlPO-EN3 (Parise J B, Stud. SurfSci. Catal., 24: 271-278, 1985); [Ga—P—O]-AEN (Glasser F P, et al., ActaCrystallogr., C50:848-850, 1994); AlPO-53(A) (Kirchner R M, et al.,Microporous and Mesoporous Materials, 39: 319-332, 2000); AlPO-53(B)(Kirchner R M, et al., Microporous and Mesoporous Materials, 39:319-332, 2000); CFSAPO-1A (He H, et al., J Incl. Phenom., 5: 591-599,1987); JDF-2 (Chippindale A M, et al., Acta Crystallogr., C50:1537-1540, 1994); MSC-1 (Simmen A, et al., Ph.D. Thesis, ETH Zurich,Switzerland, 1992); UiO-12-500 (Kongshaug K O, et al., Microporous andMesoporous Materials, 39: 333-339, 2000); UiO-12-as (Kongshaug K O, etal., Microporous and Mesoporous Materials, 39: 333-339, 2000); AlPO-8(Dessau R M, et al., Zeolites, 10: 522-524, 1990; Richardson Jr J W,Zeolites, 12: 13-19, 1992); MCM-37 (Chu C T W, U.S. Pat. No. 5,091,073,1992); Afghanite (Barian P, et al. Bull. Soc. Fr. Mineral. Cristallogr.91: 34-42, 1968; Merlino S, et al. Zeolite 1976, Program and Abstracts,Tucson Ariz., 1976; Pobedimskaya E A, et al. Dokl. Akad. Nauk SSSR 320:882-886, 1991; Ballirano P, et al. Eur. J. Mineral 9: 21-31, 1997);AlPO-5 (Bennett J M, et al. ACS Sym. Ser.218: 109-118, 1983; U.S. Pat.No. 4,310,440, 1982); CoAPO-5 (Chao K J, et al. J. Chem. Soc., FaradayTrans. 88: 2949-2954, 1992); CrAPO-5 (Radaev S, et al. J Mater. Chem.6:1413-1418, 1996); SAPO-5 and its compositional variants (Flanigen E M,et al. Pure Appl. Chem 58: 1351-1358, 1986; Flanigen EM, et al. In Proc.7^(th) Int. Zeolite Conf., Japan, pp. 103-112, 1986); SSZ-24 (Bialek R,et al., Zeolites 11: 438-442, 1991); TPAF AlPO-5 (Qiu S, et al. Zeolites9:440 -444, 1989); AlPO-14 (Broach R W, et al. In Proc. 12^(th) Int.Zeolite Conf., USA, pp. 1715-1722, 1999); GaPO-14 (Parise J B, et al.Acta Crystallogr. C42: 670-673, 1986); AlPO-41 (Kirchner R M, et al.Zeolites 14:523-528, 1994); SAPO-40 (Estermann M A, et al. J. Appl.Crystallogr. 25:539-543, 1992; Dumont N, et al. Microporous Materials 1:149-160, 1993; McCusker L B, et al. Microporous Materials 6:51-54,1996); AlPO-40 (Ramaswamy V, et al. Microporous and Mesoporous Materials31:1-8, 1999); CoAPSO-40 and ZnAPSO-40 (Lourence J P, et al. ??Journal??38:267-278, 2000); MAPSO-46 (Bennett J M, et al. Stud. Surf. Sci. Catal.37:269-279, 1988); AlPO-52 (Bennett J M, et al. Stud. Surf. Sci. Catal.49:731-739, 1989; McGuire N K, et al. Zeolites 15:460-469, 1995);SAPO-56 (Wilson S T, et al. Microporous and Mesoporous Materials28:125-137, 1999); SSZ-16 (Lobo R F, et al. Chem. Mater. 8:2409-2411,1996); CoAPO-50 (Bennett J M, et al. Stud. Surf Sci. Catal. 37: 269-279,1988); MgAPO-50 (Akolekar D B, et al. Zeolites 15: 583-590, 1995);AlPO-H2 (Li H X, et al. Chem. Commun. ??Vol??: 403-405, 1993; Kennedy GJ, et al., Solid State Nuc. Mag. Res 4: 173-178, 1995); Analcime (TaylorW H Z Z. Kristallogr 74:1-19, 1930; Knowles C R, et al. Indian Mineral.6:127-, 1965; Ferraris G, et al. Z. Kristallogr. 135: 240-252, 1972);[Al—Co—P—O]-ANA (Feng P Y, et al. Nature 388: 735-741, 1997);[Al—Si—P—O]-ANA (Artioli G, et al. Acta Crystallogr. C40:214-217, 1984);[Ga—Ge—O]-ANA (Bu X, et al. J. Am. Chem. Soc. 120:13389-13397, 1998);|Cs—Na—(H₂O)|[Ga—Si—O]-ANA (Yelon W B, et al. Zeolites 10:553-558,1990); |Cs₁₆|[Cu₈Si₄₀O₉₆]-ANA (Heinrich A R, et al. Acta Crystallogr.C47:237-241, 1991); |K—|[B—Si—O]-ANA (Millini R, et al. MicroporousMaterials 1:9-15, 1993); AlPO-24 (Wilson S T, et al. J. Am. Chem. Soc.104:1146-1147, 1982); AlPO₄-pollucite (Keller E B, Ph.D. Thesis, ETHZurich, Switzerland, 1987); Ammonioleucite (Hori H, et al. Am. Mineral.71:1022-1027, 1986); Ca-D (Ames L L, et al. Am. Mineral. 43:476-480,1958); Cs beryllosilicate pollucite (Torres-Martines L M, et al., JSolid State Chem. 51: 100-103, 1984); Cs, Fe silicate pollucite (Kopp OC, et al. Am. Mineral.48:100-109, 1963); Hsianghualite (Wen-Hui H, etal. Am. Mineral. 44:1327-1328, 1959); Kehoeite (McConnell D, et al. Can.Mines. 12:352-, 1974); Leucite (Peacor D R, Z. Kristallogr. 127:213-224, 1968); Na—B (Barrer R M, et al. J. Chem. Soc. ??vol??:1561-1571, 1952); Pollucite (Nel H J, Am. Mineral. 29: 443-451, 1944);Synthetic analcime (Ghobarker H, et al. Cryst. Res. Technol. 1071-1075,1986); Synthetic hsinghualite (Ghobarker H, et al. Annal. Chemie,Science Materiaux 24:209-215, 1999); Synthetic wairakite (Ghobarker H,et al. Cryst. Res. Technol. K90-92, 1985); Wairakite and additionalcompositional variants (Takeuchi Y. et al. Am. Mineral., 64: 993-1001,1979); AilPO-C (Bennett J M, et al. Zeolites 6:349-359, 1986; Keller EB, et al. Solid State Ionics 43: 93-103(?), 1990; AlPO-H3 (Pluth J J, etal. Acta Crystallogr. C42:1118-1120, 1986); AlPO-D (Keller E B, et al.Solid State Ionics 43:93-103, 1990); AlPO-16 (Bennett J M, et al.,Zeolites 11:502-506, 1991); Octadecasil (Caullet P, et al. Eur. J. SolidState Inorg. Chem. 28:345-361, 1991); ASU-7 (Li H, et al. J. Am. Chem.Soc. 120:10569-10570, 1998); MAPO-39 (McCusker L B, et al. ActaCrystallogr. A46:C59(?), 1990; Baur W H, et al. Z. Kristallogr.214:154-159, 1999); AlPO-31 (Bennett J M, et al. Zeolites 12:338-342,1992; Baur W H, et al. Acta Crystallogr. B50: 290-294, 1994); SAPO-31(Flanigen E M, et al. Pure Appl. Chem. 58:1351-1358, 1986; Flanigen E M,et al. In Proc. 7^(th) Int. Zeolite Conf, Japan, pp. 103-112, 1986; BaurW H, et al. Acta Crystallogr. B50:290-294, 1994); MAPO-36 (Smith J V, etal. Zeolites 13: 166-169, 1993); AlPO-12-TAMU (Rudolf PR, et al. J Phys.Chem. 90:6122-6125, 1986); AlPO-33 (Smith J V, et al. PRIVATE COMMUNIC;Patton R L, et al. U.S. Pat. No. 4,473,663, 1984); AlPO-25 (RichardsonJr J W, et al., J Phys. Chem. 94: 3365-3367, 1990); [Ga—P—O]-ATV (PariseJ B, Chem. Communic. ??vol??:606-607, 1985); AlPO-21 (Bennett J M, etal. Inorg. Chem. 24:188-193, 1985; Parise J B, et al. Acta Crystallogr.C41:515-520, 1985); [Ga—P—O]-ATV (Parise J B, Chem. Communic. 606-607,1985); AlPO-22 (Richardson Jr J W, et al. Naturwiss. 76:467-469, 1989);Beta (Higgins J B, et al. Zeolites 8:446-452, 1988; Newsam J M, et al.Proc. R. Soc. Lond. A 420: 375-405, 1988); [B—Si—O]-*BEA (Marler B, etal. In Proc. 9^(th) Int. Zeolite Conf., pp. 425-432, 1993; Reddy K S N,et al. J Incl. Phenom. Mol. Recogn. Chem. 20:197-210, 1994);[Ga—Si—O]-*BEA (Reddy K S N, et al. J Incl. Phenom. Mol. Recogn. Chem.20:197-210, 1994); CIT-6 (Takewaki T, et al. Topics in Catalysis9:35-42, 1999); Tschernichite (Boggs R C, et al. Am. Mineral.78:822-826, 1993); Bikitaite (Kocman V, et al., Am. Mineral. 59:71-78,1974; St{dot over (a)}hl K, et al. Zeolites 9:303-311, 1989);|Ca—|[Al—Si—O]-BIK (Annehed H, et al. Z. Kristallogr. 166:301-306,1984); Triclinic bikitaite (Bissert G, et al. N. Jb. Miner. Mh.??vol??:241-252, 1986); Boggsite (Pluth J J, et al. Am. Mineral.75:501-507, 1990); Beryllophosphate-H (Harvey G, Z. Kristallogr.182:123-124, 1988; Harvey G, et al. Z. Kristallogr. 201:113-123, 1992);Linde Q (Andries K J, et al. Zeolites 11:124-141, 1991); STA-5 (PatinecV, et al. Chem. Mater. 11:2456-2462, 1999); Brewsterite (Perrotta A J,et al. Acta Crystallogr. 17:857-862, 1964; Schlenker J L, et al. ActaCrystallogr. B33:2907-2910, 1977); Ba-dominant brewsterite (Cabella R,et al. Eur. J. Mineral. 5:353-360, 1993); CIT-4 (Khodabandeh S, et al.Microporous and Mesoporous Materials 11: 87-95, 1997); Syntheticbewsterite (Ghobarker H, et al. German Patent AZ 198 24 184.4-41, 1997);Cancrinite (Pauling L, Proc. Natl. Acad. Sci. 16:453-459, 1930; JarchowO, Z. Kristallogr. 122:407-422, 1965); [Al—Ge—O]-CAN (Belokoneva E L, etal. Sov. Phys. Crystallogr. 31:516-519, 1986); [Ga—Si—O]-CAN (Newsam JM, et al. Zeolites 7:569-573, 1987); [Zn—P—O]-CAN (Yakubovich O V, etal. Crystallogr. Reports 39:564-568, 1994); Basic cancrinite (Barrer RM, et al. J. Chem. Soc. 1561-1571, 1952; Bresciana Pahor N, et al. ActaCrystallogr. B38:893-895, 1982); Cancrinite hydrate (Wyart J, et al.Compt. Rend. 229:131-, 1949); Davyne (Hassan I, et al. Can. Mineral.28:341-349, 1990); ECR-5 (Vaughn D E W, E. Patent A-190,90; 1986);Microsommite (Bonaccorsi E, et al. Phys. Chem. Mineral. 22:367-374,1995); Synthetic cancrinite (Smolin Y I, et al. Kristallografiya26:63-66, 1981); Tiptopite (Peacor D R, et al., Am. Mineral.,72:816-820, 1987); Vishnevite (Hassan I, et al. Can. Mineral.22:333-340, 1984); Cesium aluminosilicate (Araki T Z, Z. Kristallogr.152:207-213, 1980); CIT-5 (Wagner P, et al. Chem. Commun. 2179-2180,1997; Yoshikawa M, et al. J Phys. Chem. B 102:7139-7147, 1998);C-Ga-Phosphate-5 (Chippindale A M, et al. Zeolites 18:176-181, 1997);C-Ga-Phosphate-6 (Cowley A R, et al. Microporous and MesoporousMaterials 28:163-172, 1999); [Zn—Ga—P—O]-CGS (Cowley A R, et al.Microporous and Mesoporous Materials 28:163-172, 1999); TNU-1 (Hong S B,et al. J. Mater. Chem. 9:2287-2289, 1999); [Ga—Si—O]-CGS (Hong S B, etal. J Mater. Chem. 9:2287-2289, 1999); TsG-1 (Lee Y J, et al. J Mater.Chem. 11:879-880, 1999); [Ga—Si—O]-CGS (Lee Y J, et al. J Mater. Chem.11:879-880, 1999); Chabazite (Dent L S, et al. Nature 181:1794-1796,1958; Smith J V, et al. Acta Crystallogr. 16:45-53, 1963);[Al—Co—P—O]-CHA (Feng P Y, et al. Nature 388:735-741, 1997);[Co—Al—P—O]-CHA (Feng P Y, et al. Nature 388:735-741, 1997; Feng P, etal. Microporous and Mesoporous Materials 23:221-229, 1998);[Mg—Al—P—O]-CHA (Feng P, et al. Microporous and Mesoporous Materials23:221-229, 1998); AlPO-34 (Harding M M, et al. ActaCrystallogr.C50:852-854, 1994); CoAPO-44 (Bennett J M, et al. Stud.Surf. Sci. Catal 37:269-279, 1988); CoAPO-47 (Bennett J M, et al. Stud.Surf. Sci. Catal. 37:269-279, 1988); Dehydrated Na-Chabazite (Mortier WJ, et al. Mater. Res. Bull. 12:241-250, 1977); GaPO-34 (Schott-Darie C,et al. Stud. Surf. Sci. Catal. 84:101-108, 1994); LZ-218 (Breck D W, etal. U.S. Pat. No. 4,333,859, 1982); Linde D (Breck D W, et al. U.S. Pat.No. 2,950,952, 1960; Lillerud K P, et al. J. Chem. Soc., FaradayTransactions 90:1547-1551, 1994); and/or the other framework minerals,both natural and synthetic, a table of which appears below. TABLE 4 Pageor Name of Zeolite First Author Cited Citation Vol. Number Year Linde RMilton R M British Patent   841,812 1960 MeAPO-47 Bennett J M, et al.Stud. Surf. Sci. Catal. 37: 269-279 1988 Flanigen E M, et al. Pure Appl.Chem. 58: 1351-1358 1986 Flanigen E M, et al. In Proc. 7^(th) Int.Zeolite 103-112 1986 Conf., Japan MeAPSO-47 Bennett J M, et al. Stud.Surf. Sci. Catal. 37: 269-279 1988 Flanigen E M, et al. Pure Appl. Chem.58: 1351-1358 1986 Flanigen E M, et al. In Proc. 7^(th) Int. Zeolite103-112 1986 Conf., Japan Phi Lillerud K P, et al. J. Chem. Soc.,Faraday 90: 1547-1551 1994 Transactions Grose R W, et al. U.S. Pat. No.4,124,686 1978 SAPO-34 Lok, B M, et al. J. Am. Chem. Soc. 106: 6092-6093 1984 SAPO-37 Pluth J J, et al. J. Phys. Chem. 93: 6516-65201989 Si-CHA Díaz-Cabañas M J, et Chem. Commun. 1881-1882 1998 al.Willhendersonite Tillmanns E, et al. N. J.. Miner. Mh. 547-558 1984ZK-14 Kuehl G H PRIVATE COMMUNICATION Kuehl G H In Molecular Sieves,85-91 1968 (ed. R. M. Barrer) ZYT-6 Ito M, et al. Acta Crystallogr.C41:   1698-1700 1985 Herschelite Discredited Chiavennite Tazzoli V, etal. Eur. J. Mineral.  7: 1339-1344 1995 Cloverite Esterman M, et al.Nature 352:  320-323 1991 CIT-1 Lobo R F, et al. J. Am. Chem. Soc. 117: 3764-3779 1995 SSZ-26 Lobo R F, et al. J. Am. Chem. Soc. 117:  3764-37791995 Lobo R F, et al. Science 262:  1543-1546 1993 SSZ-33 Lobo R F, etal. J. Am. Chem. Soc. 117:  3764-3779 1995 Lobo R F, et al. Science262:  1543-1546 1993 Chiral Rajic N, et al. Zeolites 15: 672-678 1995Zincophosphate Harrision W T A, et al. Chem. Mater.  8: 145-151 1996Dachiardite Gottardi G, et al. Z. Kristallogr. 119:  53-64 1963Vezzalini G Z Z. Kristallogr. 166:  63-71 1984 Svetlozarite DiscreditedGellens L R, et al. Mineral. Mag. 45: 157-161 1982 Deca-dodecasil 3RGies H Z. Kristallogr. 175:   93-104 1986 Sigma-1 Stewart A, et al.Stud. Surf. Sci. Catal. 37: 57-64 1988 ZSM-58 Valyocsik E W U.S. Pat.No. 4,698,217 1987 Ernst S, et al. In Zeolites for the 8^(th) IZC 55-561989 Nineties, Recent Progress Reports - Abstracts DAF-1 Wright P A, etal. Chem. Commun. 633-635 1993 DAF-2 Chen J, et al. Angew. Chem., Int.Ed. 33: 639-640 1994 ACP-3 Bu X, et al. J. Solid State Chem. 136: 210-215 1998 UCSB-3GaGe Bu X, et al. J. Am. Chem. Soc. 120:  13389-133971998 UCSB-3ZnAs Bu X, et al. J. Solid State Chem. 136:  210-215 1998UiO-20 Kongshuang K O, et al. Chem. Mater. 12: 1095-1099 2000 Dodecasil1H Gerke H, et al. Z. Kristallogr. 166:  11-22 1984 UTD-1F Wessels T, etal. J. Am. Chem. Soc. 121:  6242-6247 1999 UTD-1 Lobo R F, et al. J. Am.Chem. Soc. 119:  8474-8484 1997 TMA-E (Aiello and Aiello R, et al. J.Chem. Soc. (A). 1470-1475 1970 Barrer) Meier W M, et al. J. Solid StateChem. 37: 204-218 1981 Bellbergite Rüdinger B, et al. Miner. Petrol. 48:147-152 1993 Edingtonite Taylor W H, et al. Z. Kristallogr. 86: 53-641933 Galli E Acta Crystallogr. B32:   1623-1627 1976 Kvick Å, et al. J.Chem. Phys. 79: 2356-2362 1983 [Co—Al—P—O]-EDI Bu X, et al. Chem. Mater.10: 2546-2551 1998 [Co—Ga—P—O]-EDI Bu X, et al. Chem. Mater. 10:2546-2551 1998 K—F Barrer R M, et al. J. Chem. Soc. 2882-2891 1956Baerlocher Ch, et al. Z. Kristallogr. 140:  10-26 1974 Linde F Sherman JD ACS Sym. Ser. 40: 30-42 1977 Synthetic Ghobarker H, et al. Cryst. Res.Technol. 32: 653-657 1997 edingtonite Tetragonal Mazzi F, et al. N. Jb.Miner. Mh. 373-382 1984 edingtonite Zeolite N Christensen A N, et al.Acta Chemica Scand. 51: 969-973 1997 EMC-2 Delprato F, et al. Zeolites10: 546-552 1990 Baerlocher Ch, et al. Microporous Materials  2: 269-2801994 CSZ-1 Barrett M G, et al. UK Patent GB 2,076,793 1981 ECR-30 VaughnD E W E Patent 0,351,461 1989 ZSM-20 Newsam J M, et al. Chem. Commun.493-495 1989 ZSM-3 Kokotailo G T, et al. Adv. Chem. Ser. 101:  109-1211971 Epistilbite Kerr I S Nature 202:  589 1964 Perrotta A J Mineral.Mag. 36: 480-490 1967 Alberti A, et al. Z. Kristallogr. 173:  257-2651985 Yang P, et al. Eur. J. Mineral.  8: 263-271 1996 SyntheticGhobarkar H Cryst. Res. Technol.     151-1573(?) 1984 epistilbiteErionite Staples L W, et al. Mineral. Mag. 32: 261-281 1959 Kawahara A,et al. Bull. Soc. Fr. Minéral. 92: 250-256 1969 Cristallogr. Gard J A,et al. In Proc. 3rd Int. Cong. 94-99 1973 Molecular Sieves AlPO-17 PluthJ J, et al. Acta Crystallogr. C42:   283-286 1986 Flanigen E M, et al.Pure Appl. Chem. 58: 1351-1358 1986 Flanigen E M, et al. In Proc. 7^(th)Int. Zeolite 103-112 1986 Conf. LZ-220 Breck D W, et al. U.S. Pat. No.4,503,023 1985 Linde T Breck D W Zeolite Molecular 173 1974 Sieves ERS-7Campbell B J, et al. Chem. Commun. 1725-1726 1998 Millini R, et al. InProc. 12^(th) Int. Zeolite 541-548 1999 Conf. EU-1 Casci J L, et al.U.S. Pat. No. 4,537,754 1985 Briscoe N A, et al. Zeolites  8: 74-76 1988TPZ-3 Sumitani K, et al. E Patent EP 51318 1982 ZSM-50 Rohrbaugh W JPrivate communication Faujasite Bergerhoff G, et al. N. Jb. Miner. Mh.193-200 1958 Baur W H Am. Mineral. 49: 697-704 1964 [Al—Ge—O]-FAU BarrerR M, et al. J. Chem. Soc. 195-208 1959 [Co—Al—P—O]-FAU Feng P Y, et al.Nature 388:  735-741 1997 [Ga—Ge—O]-FAU Barrer R M, et al. J. Chem. Soc.195-208 1959 Beryllophosphate Gier T E, et al. Zeolites 12: 770-775 1992X CSZ-1 Barrett M G, et al. UK Patent BG 2,076,793 1981 ECR-30 Vaughn DE W E Patent 0,351,461 1989 LZ-210 Breck D W, et al. U.S. Pat. No.4,503,023 1985 Linde X Milton R M U.S. Pat. No. 2,882,244 1959 Olson DH, et al. J. Phys. Chem. 74: 2758-2764 1970 Linde Y Breck D W U.S. Pat.No. 3,130,007 1964 Costenoble M L, et al. J. Chem. Soc., Faraday 72:1877-1883 1976 Trans. I SAPO-37 Lok B M, et al. J. Am Chem. Soc. 106: 6092-6093 1984 Siliceous Na—Y Hriljac J J, et al. J. Solid State Chem.106:  66-72 1993 ZSM-20 Newsam J M, et al. Chem. Commun. 493-495 1989ZSM-3 Kokotailo G T, et al. Adv. Chem. Ser. 101:  109-121 1971Zincophosphate X Gier T E, et al. Zeolites 12: 770-775 1992 FerrieriteVaughn P A Acta Crystallogr. 21: 983-990 1966 [Ga—Si—O]-FER Jacob N E,et al. Zeolites 13: 430-434 1993 [Si—O]-FER Gies H, et al. Zeolites  7:442-445 1987 Morris R E, et al. J. Am. Chem. Soc. 116:  11849-11855 1994FU-9 Seddon D, et al. E Patent  B-55,529 1985 ISI-6 Morimoto N, et al.U.S. Pat. No. 4,578,259 1986 Monoclinic Gramlich-Meier R, et Am.Mineral. 70: 619-623 1985 ferrierite al. NU-23 Whittam T V E PatentA-103-981 1984 Sr-D Barrer R M, et al. J. Chem. Soc. 2296-2305 1964ZSM-35 Plank C J, et al. U.S. Pat. No. 4,016,245 1977 FranziniteBallirano P, et al. Can. Mineral. 38: 657-668 2000 Gismondine Fischer K,et al. Adv. Chem. Ser. 101:  250-258 1971 [Al—Co—P—O]-GIS Feng P Y, etal. Nature 388:  735-741 1997 [Co—Al—P—O]-GIS Feng P, et al. Microporousand 23: 221-229 1998 Mesoporous Materials [Co—Ga—P—O]-GIS Cowley A R, etal. Chem. Commun. 673-674 1996 [Co—P—O]-GIS Yuan H M, et al. Inorg.Chem. 39: 1476-1479 2000 [Ga—Si—O]-GIS Cho H H, et al. Chem. Mater. 12:2292-2300 2000 [Mg—Al—P—O]-GIS Feng P, et al. 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The zeolites may be used for oral chelation therapy for heavy metalpoisoning, either by natural means such as Wilson's disease and primarybiliary cirrhosis, or from environmental exposure such as lead poisoningand intoxication by other various heavy metals such as arsenic,chromium, cesium and strontium including also ammonia, mercaptans andother plant-, marine organism- and nuclear-derived toxins and involvingmultiple administrations during a single day, single daily, orsequential daily administrations for months to years to slowly removetissue-bound toxins from the bodies of humans.

The zeolites may be used for therapy for hepatic encephalopathy as anadjunct or alternative to other therapies currently used by binding upchemical mediators of hepatic encephalopathy, which include at leastammonia and mercaptans which are elevated due to poor function of theliver because of its diseased state, which are bound to the zeolite inthe gastrointestinal tract and are then removed from the body by fecalelimination. Examples of mercaptans include hydrogen sulfide and alkylsulfides.

The zeolites may be used in the event of radioactive contamination offood (specifically strontium or cesium, but also other contaminatingradionuclides) such that the zeolite is ingested and the radionuclide isadsorbed by the zeolite and carried out of the body (the radionuclidethereby not being absorbed and finding its way into bone or soft tissuewhere the half-life is substantially prolonged).

The zeolites may be used for treating potassium depletion for patientswith elevated potassium in the outpatient or hospital by exploitingtheir ion-exchange properties in the intestinal juices whereby excesspotassium is eliminated with the zeolite in the feces.

The zeolites may be used for oral drug delievery in which the specificframework structure, or mixture of structures chosen, or size ofparticles, to provide a temporally predictable gastrointestinalabsorption profile whereby the zeolite acts a carrier of an activepharmaceutcal ingridient which is either slowly or rapidly desorbed outof the zeolite and absorbed by the gastointestinal tract on apredictable customizable basis.

The zeolites may be used for treating osteoporosis based on theobservation that eggshell thickness increases in hens fed a smallpercentage of their diet as zeolite.

The use of zeolites as the active component for a hemoperfusion devicein which blood-borne toxins, whether from an endogenous or exogenoussource, are selectively depleted based on the relative affinity ofcertain zeolites for certain toxins may be used to advantage in asimilar way as charcoal is currently used in the hemoperfusion devices.

The zeolites may be used to mitigate against toxic consequences ofacrolein exposure in humans.

The zeolites may be used for mitigation, minimization, treatment andprevention of noxious and odoriferous flatulence exploiting theproperties of zeolites to selectively absorb hydrogen sulfide, the mostodoriferous component of flatulence.

The zeolites may be used for treating hemachromatosis alone or incombination with complementary therapies including therapeuticphlebotomy, erythropoietin administration, desferroxamine, and otherexperimental oral and intravenously administered chelating agents.

The zeolites may be used to remove arsenic and decrease toxicity fromtherapeutic arsenic-containing medications used in the treatment ofcancer and infections specifically the cardiac arrhythmia-inducingeffects of arsenic.

The zeolites may be used for therapy of acute poisonings from a widevariety of plant, animal, industrial and environmental toxins. Theseinclude the mitigation, minimization and elimination of toxin-inducedclinical syndromes affecting the cardiovascular, respiratory,gastrointestinal, hepatic, renal, hematopoietic and nervous systems fromthe following list of plants by their common name, scientific name,toxic part and specific poison: TABLE 5 Plants, toxic parts, andspecific poison Common Scientific Name Name Toxic part ToxinSymtoms/syndrome Akee Blighia sapida Fruit Hypoglycins A, B “Jamaicavomiting sickness” with hypoglycemia, convulstions, coma, lethalApricot, Prunus species Pit/seed, Amygdalin Cyanide liberation in gutand peach, etc foliage glycoside cyanide poisoning Autumn Colchicumautumnale All parts of Colchicine alkaloid Vomiting, diarrhea, shock,crocus plant death Meadow Colchicum autumnale All parts of Colchicinealkaloid Vomiting, diarrhea, shock, saffron plant death Bird ofCasealpinia gilliesii Pods Unidentified Vertigo, vomiting, paradisediarrhea, dehydration Black locust Robinia pseudoacacia Inner bark,Robin (phytotoxin), Vomiting, diarrhea, young leaves, robitin(glycoside) shock, CNS depression seeds Bleeding-heart Dicentra formosaFoliage, roots Apomorphine, Tremors, staggering gait, protoberberine,labored breathing, salivation, protopine, other convulsions, death dueto isoquinoline-type paralysis alkaloids Buckeye Aesculus speciesLeaves, Esculin (glycoside) Vomiting, diarrhea, flowers, seeds pupillarydilatation, ms. Twitching, weakness, ataxia, CNS depression, paralysisCastor bean Ricinus communis All parts, esp. Ricin, ricinine Nausea,vomiting, violent seeds (phytotoxins, purging, hemolysis, renaltoxalbumins) failure, oral burning sensation Century plant Agaveamericana Sap Unknown Skin exposure causes dermatitis associated withleukocytosis and fever Chinaberry Melia azedarach Fruit Probably aresinoid Severe gastroenteritis Christmas rose Helleborus nigerRootstock and Helleborin, Numbing sensation in leaves belleborein mouth,vomiting, diarrhea, (glycosides) convulsions, CNS effects Daphne Daphnemezereum Berries, bark, Daphnin, mezerenic Burning oral sensation,leaves acid anhydride vomiting, blood and mucus in diarrhea, renalfailure, weakness, convulsions, death Desert potato Jatropha macrorhizaPlant root Phytotoxins Nausea, vomiting, abdominal cramps, waterydiarrhea Dumb cane Dieffenbachia seguine All parts of Calcium oxalateBurning sensation of or picta plant induing crystals, toxic tongue,mouth, larynx; sap protein breathing affected Fava bean Vicia faba Bean,plant (G6PD Headache, nausea, vomiting, pollen deficiencient abdominalpain, icterus individuals) hyperthermia, hemolytic anemia, hemogloinuriaFour o'clock Mirabilis jalapa Root, seeds Trigonelline Skin, mouth,throat alkaloid irritant causing purgation Foxglove Digitalis purpureaLeaves and Digitoxin, digitalin, Cardiac arrhythmia seeds digitoninglycosides Golden chain Laburnum anagyroides Beanlike QuinolizidineDysphagia, incoordination, capsules in alkaloid cytisine vomiting,renalr failure, which seeds convulsions, coma, death by are suspendedasphyxiation Holly Ilex species Berries Ilicin Nausea, abdominal pain,severe vomiting, diarrhea Hyacinth Hyacinthus orientalis BulbNarcissine-like Digestive upset, alkaloid(s) vomiting, diarrheaHydrangea Hydrangea species All parts of Hydrangin (a Cyanide liberationin gut and plant cyanogenic glycoside) cyanide poisoning Indian tobaccoLoebelia inflata All parts of Lobeline and Nausea, vomiting, plantlobelamine weakness, tremors, alkaloids convulsions, coma, death Iris(blue flag) Iris versicolor Leaves and Irisin, inidin, GI tract, liver,pancreas; root stalks irigenin purging and congestion of GI tractJack-in-the- Arisaema triphyllium Rhizome Calcium oxalate Burningsensation of pulpit (Indian crystals tongue, mouth, larynx; turnip)breathing affected Jerusalem Solanium pseudocapsicum Berries Solanineand related Headache, abdominal pain, cherry alkaloids vomiting,diarrhea, circulatory collapase, convulsions; CNS, resp. depressionJimson weed Datura stramonium, All parts of Atropine, Intense thirst,urinary metel, inoxia, plants, hyoscyamine, retention, xerostomia,suaveolens, other species especially scopolamine tachycardia, delirium,seeds (solanaceous incoherence, pyrexia, alkaloids) confulsions, coma,death Lantana Lantana camara Berries Lantadene A Extreme muscular(unripe) (a polycyclic weakness, GI irritation, triterpinoid) lethargy,cyanosis, circulatory collapse Larkspur Delphinium ajacis, Young plant,Delphinine (?other Digestive upset, respiratory other species seedspoisonous depression, parestieias, alkaloids) salivation, headache,hypotension, cardie arrhythmias Lilly of the Convallaria majalis Leaves,Convallarin, Dizziness, vomiting, valley flowers, roots convallamarin,Cardiac arrhythmias convallatoxin (cardiac glycosides) MistletoePhoradendron species Berries b- Acute gastroenteritis, phenylethylamine,circulatory collapse, nausea, tyramine, choline vomiting, diarrhea,respiratory difficulties, bradycardia, delirium, hallucinations, comaMonkshood Aconitum napellus Roots, seeds, Aconitine (a Vagalstimulation, leaves polycyclic diterpene bradycardia, irregular pulse,and other alkaloids) dimness of vision, nausea, vomiting, diarrhea,respiratory failure, tingling/numbing of lips, tongue Morning gloryIpomoea violacea Seeds Ergine, isoergine, Pychotomimetic effects,elymoclavine (other hallucinations, euphoria, olavine alkaloids nausea,uterine related to LSD) stimulation Mountain Kalmia latifolia All partsof Andromedotoxin Stimulation then paralysis of laurel and augustifoliaplant skeletal muscle (curare-like effects), cardiac tissue inhibition,CNS depression, respiratory depression, death Narcissus/daffodilNarcissus species Bulb narcissine, lycorine Severe gastroenteritis,(other alkaloids) vomiting, purging, trembline, convulsions,hypotension, hepatic degeneration Nightshade Solanum species Varies withSolanine alkaloids See Jerusalem cherry family specie Oleander Neriumoleander All parts oleandroside, Local irritation to mucous oleandrinnerioside membranes, mouth, (cardiac glycosides) stomach; nausea,vomiting, diarrhea, slow and irregular pulse changing to rapid/threadypulse, ventricular fibrillation, death Pencil tree Euphorbia tirucalliLeaves, stems, Unidentified irritant Irritation to lips, tongue, milkysap in sap mouth; skin blisters Peyote Lophophora williamsii All partsMescaline and other Sensory distortion, visual and diffusa especiallyalkaloids hallucinations cactus “button” Philodendron Philodendronspecies Entire plant Calcium oxalate Local irritation to mucousmembranes, swelling of lips, tongue, excessive salivation, difficultywith swallowing; swelling of tongue, pharynx, inhibits respirationCaladium Caladium bicolor Entire plant Calcium oxalate Local irritationto mucous membranes, swelling of lips, tongue, excessive salivation,difficulty with swallowing; swelling of tongue, pharynx, inhibitsrespiration Elephant ear Colocasia antiquorum Entire plant Calciumoxalate Local irritation to mucous membranes, swelling of lips, tongue,excessive salivation, difficulty with swallowing; swelling of tongue,pharynx, inhibits respiration Hemlock Conium maculatum All parts ofConiium (alkaloid) Nausea, vomiting, early (poison) plant CNSstimulation followed by severe CNS depression, assoc. muscle paralysis,repiratory failure Poison ivy Toxicodendron radicans All parts ofUrushiol (comprised Severe dermatitis with (erroneously or Rhustoxicodendron plant of phenolic substances inflammation, vesicles,called poison including including 3-N- blistering oak) smoke frompentadecylcatechol burning Pokeweed Phytolacca amnericana Roots, leavesSaponin, a Burning sensation in mouth, (also called and decandra andfruit glycoprotein, GI cramps, vomiting, pigeonberry, phytolaccine,diarrhea; visual disturbance, inkberry) phytolaccotoxin amblyopia,perspiration, (alkaloids) salivation, lassitude, prostration, weakendrespiration and pulse, death Privet Ligustrum japonicum All partsPossible Vomiting, colic, diarrhea, andromedotoxin, death probablyunknown Red squill Urginea maritima Bulb Cardiac glycosides (seeOleander) Rhododendron Rhododendron All parts Andromedotoxin Salivation,nasal discharge, (azaela) species nausea, vomiting, diarrhea, muscleweakness, labored breathing, coma; dullness of vision, paralysis,hypotension, lacrimation, anorexia Rhubarb Rheum rhaponticum Leaf bladeOxalic acid Severe intermittent (not petiole) abdominal pains, vomiting,diarrhea, headache, weakness, hemorrhages; hypocalcemia causing muscularcramps, tetany; convulsions, coma, death by renal failure Rosary peaAbrus precatorius Seeds Abrin (phytotoxin), Burns to mouth, esophagus;(crabseye, abric acid (tetanic like castor bean; nausea, precatoryglycoside) vomiting, severe diarrhea, bean, jequirity weakness, shock,trembling bean, Indiian hands, oliguria, hemolytic licorice) anemia,hallucinations, fatal uremia Star-of- Ornithogalum umbrellatum All partsColchicine-related Nausea, nervous Bethlehem alkaloids symptoms, general(snowdrop) disturbances of GI tract Sweet pea Lathyrus odoratus SeedsAminopropionitrile Skeletal deformity and growth suppression; muscleparalysis Texas Sophora secundiflora Entire plant Cytisine Increasedsalivation, nausea, mountain vomiting, headache, vertigo, laurelconfusion, hallucinations, excessive thirst, muscle fasciculation,convulsion, respiratory stimulation then failure Threadleaf Seneciolongilobus Entire plant Pyrrolizidine Chronic ingestion causes groundsel(ingested as alkaloids enlarged liver, ascites, herbal tea) abdominalpain, headache, apathy, emaciation; major cause of veno-occlusivedisease Tobacco Nicotiana species Possibly all Nicotine and relatedNausea, vomiting, parts alkaloids muscular fasciculations, early CNSstimulation followed by severe CNS depression assoc. with muscleparalysis and respiratory failure Water Cicuta maculata All parts,Cicutoxin Severe stomach pain, hemlock and other species mostly thegreat mental excitation (cowbane) roots and frenzy, vomiting,salivation, violent spasmodic convulsions alternating with periods ofrelaxation, dilated pupils, delirium, death Wisteria Wisteria floribundaSeeds or pods Wisterin (glucoside) Mild to severe (Japanese); W.sinensis gastroenteritis, vomiting, (Chinese) abdominal pain, diarrheaYellow Gelsmium semperviren Whole plant, Gelsemine and Depress andparalyze jessamine berries gelseminine nerve motor endings in (Carolina(alkaloids) brain and spinal cord, jessamine) respiratory arrest YellowThevetia peruviana All parts; fruit Thevetin A, B; Similar to Oleander;Local oleander “lucky nut” thevetoxin (cardiac irritation to mucousglycosides) membranes, mouth, stomach; nausea, vomiting, diarrhea, slowand irregular pulse changing to rapid/thready pulse, ventricularfibrillation, death Yew Taxus beccata All parts, esp. Taxine (alkaloid)Nausea, vomiting, diarrhea, and T. canadensis seeds abdominal pain,circulatory failure, difficulty breathing; depresses heart function;dermatitis

The zeolites may be used for treating the following food-bornetoxin-induced diseases: cholera, botulism and food poisoning due toBacillus cereus and staphylococcal poisons and Escherecia coli; thefollowng toxic marine ingestions: (1) paralytic shellfish poisoning fromthe ingestion of mussels (Mytilus edulis and Mytilus californianus),clams (Saxidomus gigantus [the Alaskan butter clam] and Mya arenaria[the “soft-shell clam”]), scallops (Placopecten magellanicus), oysterswhich had previous fed upon certain Gonyaulux species (which comprisethe so-called “red tide”) and elaborate saxitoxin 1, neosaxitoxin 2,gonyautoxin 3, gonyautoxin 4 and gonyautoxin 5; (2) pufferfish poisoning(“fugu” in Japan, tambore puffer in China); and (3) ciguatera, fromcertain fish (such as barracuda, amberjack, kingfish and dolfin) exposedto the benthic dinoflagellate Gambierdiscus toxicus; and minimization,mitigation and treatment of any one of the several sydromes arising fromthe ingestion of toxic mushrooms including stages I, II and IIIgastroenteritis and hepatorenal syndrome, the anti-cholinergic syndrome,delayed gastroenteritis with CNS abnormalities, cholinergic syndrome,the disulfiram-like reaction with alcohol, hallucinations, delayedgastritis and renal failure and the general gastroenteritis syndromes ofnausea, vomiting, abdominal cramping and diarrhea; binding of one ormore of the following mushroom poisonous substances including thecyclopeptides amatoxins and phallotoxins, muscimol, ibotenic acid[2552-55-8], gyromitrin monomethyl hydrazine, muscarine, coprine, indolespecies, orelline, orellanine, psilocin, psilocybin; for one or more ofseveral different mushroom species including Amanita muscaria (alsoknown as “fly agaric”),pantherina, gemata, cokeri, cothurnata,phalloides (also known as the “death cap”), verna (also known as the“death angel”), virosa (also known as the “destroying angel”),bisporigera, ocreata, suballiacae, tenuifolia; Galerina autumnaluis,marginata, venerata; Lepiota helveola, vosse-randii, Conocybe filaris,Gyromitra esculenta (also known as the “false morel”), gigas, ambigua,infula, cardiniana, brunnea; Paxina species; Sarcosphera coronaria;Boletus calopus, luridus, pulcherimus, satanas; Clitocybe clavipes,cerrusata, dealbata, illudens, riuulosa; Inocybe fastigiata, geophylla,lilocina, patuoillaridi, purica, rimosis; Psilocybe cubensis,caerulescens, cyanescens, baeocystis, fimentaria, mexicana, pellulolosa,semilanceata, silvatica; Conocybe cyanopus; Gymnopilus aeruginosa,spectabilis, validipes; Panaeolus subbalteatus andfoenisecii (also knownas the “mowers' mushroom”); Stropharis coronillal; Cortinariusorellanus, speciosissimus, splendoma, gentilis; Chlorophyllummolybdites; and Orphalates illudens (also known as the “jack-o-lantern”mushroom).

Dosage and Administration

Preferred dosages are 100-1000 mg sodium aluminosilicate zeolite to a5-20 kg weight of the human for treating lead poisoning. If the drug isadministered to children, the preferred formulation would be as agelatin capsule with minimal to no water. The number of times it wouldbe administered could be up to 4× per day and could go on daily for morethan 1 year. Actual dosage amounts could vary substantially depending onconventional criteria.

For treating excess ammonia, preferred dosages may be about 10 grams toa 70 kg human. This could be up to 4× per day and would be used for upto about 7 days per episode of ammonia-induced encephalopathy. Actualdosage amounts could vary substantially depending on conventionalcriteria. Preferably, a zeolite formulation would be administeredbetween meals.

The particle size graphs of FIGS. 1-2 show the binding of ammonia usingthe same mass of sodium aluminosilicate, but with different particlesize distributions. It shows that the smaller the particle, the poorerthe ammonia binding. Hence, the larger the particle, the more active thedrug in binding ammonia. However, there is a practical upper limit forparticle size, and that upper limit is palatability. One must strike theright balance that optimizes the trade-off between ammonia bindingpalatibility. Preferably, at least 90% of the particles are of particlesize from about 90 μm to about 150 μm. More preferably, at least 95% ofthe particles are in that range.

The following table present toxicology data on sodium aluminosilicates.TABLE 6 Toxicology Studies by Oral Gavage Performed with SodiumAluminosilicate Study Animal Author/ Toxico- Company logy Dose ReportModel Schedule Range Findings Notes References Degussa, Rat Single 5,000mg/kg to No Degussa A G - US IT No. 78-0012- 1978 dose 31,800 mg/kgMortality DKT (unpublished data, 1978) observed Gloxhuber, Rat GloxhuberCh, Potokar M, 1983 Pittermann W, et al. Food Chem. Toxic. 21: 209-220(1983) Gaynor, Rat Gaynor T, Klusman L. Procter & 1973 Gamble Company;Human Safety Appendices on Sodium Aluminosilicate, A.2 (1973) Thomas,Rat Thomas J, Ballantyne B; J. of Am. 1992 Coll. Of Tox. 11(3): 259-273(1992) Moore, Rat Moore G E, Huntingdon Research 1974 Center, ProjectNo. 747-129 in: Procter & Gamble Company; Human Safety Appendices onSodium Aluminosilicate, A.2 (1974) Moulton, Rat Moulton R H, ScientificAssociates, 1974 Inc., S. A. No. 201935 in: Procter & Gamble Company;Human Safety Appendices on Sodium Aluminosilicate, A.2 (1973) Degussa,Rat Degussa A G - US IT No. 88-0207- 1988 DKT (unpublished data, 1988 A)Litton, Rat Litton Bionetics, Inc.“Mutagenic 1974 evaluation of compoundFDA 71- 45, synthetic sodium silicoaluminate,” prep, for FDA; NTIS, USDept. of Commerce, Springfield, VA; PB 245 468 (1974) Huber, Rat J. M.Huber Corporation; Report 1973 date January 12, 1973 (unpublished data)Degussa, Rat 5,110 mg/kg Degussa A G - US IT No. 90-0146- 1990A (GLP)DGT (unpublished data, 1990 A) Degussa, Degussa A G - US IT No. 90-0149-1990B DGT (unpublished data, 1990 D) Litton, Rat Single LD₅₀ > 5000Identical BgVV (Bundesinstitut für gesund- 1974a dose mg/kg protocol andheitlichen Verbraucherschutz und laboratory as Veterinärmedizin),Ärtzliche study below Mitteilung bei Vergiftungen 1999, ISBN3-931675-59-9 Litton, Rat Single LD₅₀ Results BgVV (Bundesinstitut fürgesund- 1974b dose 1050 deemed NOT heitlichen Verbraucherschutz undmg/kg RELIABLE by Veterinärmedizin), Ärtzliche HERA Panel Mitteilung beiVergiftungen 1999, ISBN 3-931675-59-9 Litton, Rat D × 5 5,000 mg/kg/d Nosigns Reference not provided in HERA 1974c of toxicity documentation orabnormal behavior Henkel, Mouse Single 10,000 mg/kg n/a Henkel KgaA,Archive-No. TBD 1978 dose 780104 (Akute Toxizität an der Maus, 11/1978)Sturm RN, Procter & Gamble Sturm, Dog Single n/a Company; Human Safety1973 dose Appendices on Sodium Aluminosilicate, A.3 (1973) Henkel, Rat D× 14 0.000% (w/w) No change in Henkel KgaA, Archive-No. R 1979a (Fischer0.625% (w/w) food consump- 0100197 (External Report, Tracor- 344) 1.25%(w/w) tion, no marked Jitco, Inc., June 28, 1979, 2.5% (w/w) signs ofunpublished data) 5.0% (w/w) toxicity on 10.0% (w/w) gross necropsyHenkel, Mouse D × 14 0.000% (w/w) No change in Henkel KgaA, Archive-No.R 1979b (B6C3F1) 0.625% (w/w) food 0100196 (External Report, Tracor-1.25% (w/w) consumption, no Jitco, Inc., June 28, 1979, 2.5% (w/w)marked signs of unpublished data) 5.0% (w/w) toxicity on 10.0% (w/w)gross necropsy Henkel, Rat D × 90 0 ppm High dose group: Henkel KgaA,Archive-No. TBD 1977 (Wistar) (w/w) hyperplastic 770012 Subacute oraleToxizität an 1,000 ppm reaction of Ratten, 90-Tage-Test, Jan. 1977,(w/w) tranansitional unpublished data). 5,000 ppm epithelium with (w/w)calculi; kidneys 10,000 ppm of male higher (w/w) silicate content vs.ctrls; NOAEL 5,000 ppm (250-300 mg/kg/d; 1500-1800 mg/m²/d) Henkel, RatD × 163 0.0% (w/w) D28 sac: no Δ; Henkel KgaA, Archive-No. TBD 1975(COX-SD) 0.5% (w/w) D84, D85: 1 EX 0143 (External Report, Procter & 1.0%(w/w) death/day: bladder Gamble, Sept., 1975, 2.0% (w/w) tox, stones;D91 unpublished data) sac: bladder stones; high dose only; D163 sacbladder stones 1 animal each in 1.0% and 0.5% groups Henkel, Rat D × 1600.0% (w/w) UA: No Δ treated Henkel KgaA, Archive-No. TBD 1976a (COX-SD)or 0.125% (w/w) vs. Ctrl; bladder EX 0127 (External Report, Procter & D× 200 2.0% (w/w) tox, stones, xtals Gamble; June, 1976, in high doseunpublished data) group; no Δ in urine parameter or kidney function;Histopath: ↑ interstitial nephritis, regenerative epithelium and [renal]pelvic epithelial hyperplasia; bladder: ↑ transitional epitheliumhyperplasia in high dose group. No histopath Δ in low dose group; NOAEL0.125% (˜69 mg/kg/d; ˜420 mg/m²/d) Henkel, Rat D × 168 0.0% (w/w)Regarding Two citations for this study: 1976b 0.125% (w/w) mortality,physical (1) Henkel KgaA, Archive-No. (Long- (24 wk) 0.5% (w/w)appearance, feed TBD EX 0129 (External Report, Evans) 2.0% (w/w)efficiency, body Procter & Gamble, May, 1976, weights, organ unpublisheddata); weights and (2) Henkel KgaA, Archive-No. organ/body ratios TBD EX0137 (External Pathology no toxic effects Report [13 weeks], Procter &observed. Gamble, March, 1976, Histopath: unpublished data) microscopicalternations in the kidneys at 0.5% and 2.0% groups; NOAEL 0.125% (˜69mg/kg/d; ˜420 mg/m²/d) Henkel, Rat D × 728 0 ppm Mortality, feed & Samestudy as Henkel KgaA, Archive-No. SAS 1979c (Wistar) (104 wk) 10 ppmwater consumption, below, this is 7900017 (Prüfung auf 100 ppm BWmonitored; part 2 with chronischtoxische und 1000 ppm Ophth, blood, part1 below. tumorerzeugende Wirking von urinary, bio- Sasil bei einerVersuchsdauer von chemical params 2 Jahren Teil II, Sept., 1979, eval.;104 wk sac: unpublished data) all organs gross/micro eval. Nosignificant test ariticle related effects were observed on histolopath;no Δ in types or incid.of neoplasms. NOEL 60 mg/kg/d (360 mg/m²/d)Henkel, Rat D × 728 0 ppm Mortality, feed & Henkel KgaA, Archive-No. SAS1979d (Wistar) (104 wk) 10 ppm water consumption, 7900016 (Prüfung auf100 ppm BW monitored; chronischtoxische und 1000 ppm Ophth, blood,tumorerzeugende Wirking von urinary, bio- Sasil bei einer Versuchsdauervon chemical params 2 Jahren Teil I, Sept., 1979, eval.; 104 wkunpublished data) sac: all organs gross/micro eval. No significant testariticle related effects were observed on histolopath; no Δ in types orincid. of neoplasms. NOEL 60 mg/kg/d (360 mg/m²/d)

TABLE 7 Table of Genotoxicity Studies Performed with SodiumAluminosilicate Study Author/ Company Report Test Schedule StrainsFindings Notes References Zeiger, 1987 Ames w/ & w/o S9 S. typhimuriumNo mutagenicity Zeiger E, Anderson B, Haworth S, activation TA 98detected in any et al. Environmental Mutagenesis 9 TA 100 strain (suppl.9): 1-110 (1987) TA 1535 TA 1537 TA 1538 Prival, 1991 Ames S.typhimurium No mutagenicity Two sources cited TA 98 detected in any (1)Prival M J, Simmon V F, TA 100 strain Mortelmans K E, Mutat. Res TA 1535260: 321-329 (1991); TA 1537 (2) Simmon V F and Eckford S L TA 1538Microbial mutagenesis testing of substances. Compound report: F76- 001,sodium aluminum silicate. prep. for FDA; NTIS, US Dept. of Commerce,Springfield, VA; PB89- 193650 (1989) Prival, 1991 Reverse w/ & w/o S9 E.coli WP2 Two sources cited mutation activation (1) Prival M J, Simmon VF, Mortelmans K E, Mutat. Res 260: 321-329 (1991); (2) Simmon V F andEckford S L Microbial mutagenesis testing of substances. Compoundreport: F76- 001, sodium aluminum silicate. prep. for FDA; NTIS, USDept. of Commerce, Springfield, VA; PB89- 193650 (1989) Litton, 1974 S.cerevisiae Mutagenic Litton Bionetics, Inc.”Mutagenic potential notevaluation of compound FDA 71- reported 45, synthetic sodiumsilicoaluminate,” prep, for FDA; NTIS, US Dept. of Commerce,Springfield, VA; PB 245 468 (1974) Litton, 1974 H. sapiens No clastogeicLitton Bionetics, Inc.”Mutagenic embryonic lung potential observedevaluation of compound FDA 71- cell cultures 45, synthetic sodium W 38silicoaluminate,” prep. for FDA; NTIS, US Dept. of Commerce,Springfield, VA; PB 245 468 (1974) FASEB, 1977 DNA-repair NegativeFederation of American Societies of assay Experimental Biology (FASEB),“Tentative evaluatin of the health aspects of certain silicates as foodingredients” (1977), cited in How M and Solbe J, Unilever Research,Document ref. D/93/021 (1993) Litton, 1974 Male albino 4.25 mg/kg Singledose & No mutagenic Observation Litton Bionetics, Inc.”Mutagenic rat(10-12 42.5 mg/kg D × 5 potential observed time points: evaluation ofcompound FDA 71- wk old) 425 mg/kg & 6, 24, 48 hrs; 45, synthetic sodium5000 mg/kg No Δ in type silicoaluminate,” prep, for FDA; or number ofNTIS, US Dept. of Commerce, chromosomal Springfield, VA; PB 245 468(1974) aberrations observed; (+) ctrl → (+)

TABLE 8 Table of Developmental Toxicology and Teratogenicity StudiesPerformed with Sodium Aluminosilicate Study Author/ Company Report ModelSchedule Dose Levels Findings Notes References Henkel, 1978 Rat D × 10on 0 mg/kg D20 sac: high Henkel KgaA, Archive-No. R (Charles gestational74 mg/kg conception rates; 0100168 (External Report, Procter River; days6-15 1600 mg/kg no maternal, & Gamble, May, 1978 unpublished pregnant)(gavage) embryo or fetal tox data) noted; no diff in incidence of softtissue malformations or skeletal defects vs. ctrl NOAEL 1,600 mg/kg(9,600 mg/m²) FDRL, 1973 Rat D × 10 on 0 mg/kg D20 sac: no effect Foodand Drug Research (Wistar, gestational 16 mg/kg on nidation,Laboratories, Inc. Teratologic pregnant) days 6-15 74 mg/kg maternal, orfetal Evaluation of FDA 71-45 (sodium 345 mg/kg survival noted; nosilicoaluminate) prep. for FDA, 1,600 mg/kg diff in incidence of NTIS,US Dept. of Commerce, soft tissue USA, PB 223 810 (1973) malformationsor (gavage) skeletal defects vs. ctrl NOAEL 1,600 mg/kg (9,600 mg/m²)FDRL, 1973a Mouse D × 10 on 0 mg/kg D17 sac: no effect Food and DrugResearch (CD-1, gestational 16 mg/kg on nidation, Laboratories, Inc.Teratologic pregnant) days 6-15 74 mg/kg maternal, or fetal Evaluationof FDA 71-45 (sodium 345 mg/kg survival noted; no silicoaluminate) prep.for FDA, 1,600 mg/kg diff in incidence of NTIS, US Dept. of Commerce,(gavage) soft tissue USA, PB 223 810 (1973) malformations or skeletaldefects vs. ctrl NOAEL 1,600 mg/kg (4,800 mg/m²) FDRL, 1973b Rabbit(Dutch; D × 14 on 0 mg/kg D29 sac: no effect Food and Drug Researchpregnant) gestational 16 mg/kg on nidation, Laboratories, Inc.Teratologic days 6-18 74 mg/kg maternal, or fetal Evaluation of FDA71-45 (sodium 345 mg/kg survival noted; no silicoaluminate) prep. forFDA, 1,600 mg/kg diff in incidence of NTIS, US Dept. of Commerce,(gavage) soft tissue USA, PB 223 810 (1973) malformations or skeletaldefects vs. ctrl NOAEL 1,600 mg/kg (??? conversion mg/m²) Henkel, 1978Rabbit (New D × 14 on 0 mg/kg D29 sac: no effect Henkel KgaA,Archive-No. R Zealand; gestational 16 mg/kg on maternal 0100169(External Report, Procter & pregnant) days 6-18 74 mg/kg toxicity oreffect on Gamble, June, 1978 unpublished 345 mg/kg survival noted; nodata) 1,600 mg/kg diff in incidence of (gavage) soft tissuemalforma-tions or skeletal defects vs. ctrl; NOAEL 1,600 mg/kg (???conversion mg/m²) FDRL, 1973c Hamster D × 5 on 0 mg/kg D14 sac: noeffect Food and Drug Research (Syrian; gestational 16 mg/kg on nidation,Laboratories, Inc. Teratologic pregnant) days 6-10 74 mg/kg maternal, orfetal Evaluation of FDA 71-45 (sodium 345 mg/kg survival noted; nosilicoaluminate) prep. for FDA, 1,600 mg/kg diff in incidence of NTIS,US Dept. of Commerce, (gavage) soft tissue USA, PB 223 810 (1973)malformations or skeletal defects vs. ctrl NOAEL 1,600 mg/kg (???conversion mg/m²)

The following examples are offered by way of illustration and not by wayof limitation to the scope of the claims.

EXAMPLES Example 1 General Manufacturing Process

The synthesis of sodium aluminosilicate consists of one syntheticreaction of aluminum oxide (Al₂O₃) (which is dissolved in hot sodiumhydroxide in Step I) with liquid sodium silicate (Na₄SiO₄) at ambienttemperature, to yield the crude sodium aluminosilicate crystallinesubstance (Step II). The crude crystals are then size reduced byconventional roller milling and size selected (Step III) yielding auniform granular material. The material is collected in 40 cu. ft. bulkbags (Step IV) and manually transferred to a second size selection stepfor final size selection (Step V). The resulting size selection processyields a still more uniform particle size distribution of ca. 95% of thecrystalline material ranging between 90 and 150 micrometers (μm).

The properly size selected material is washed in a clarification step inwhich an optimized retrograde flow rate of reverse osmosis (RO) waterpartially purifies and pH adjusts the crystalline material (Step VI).The material is then gravity-drained and dried with vacuum assistance.The partially purified, pH adjusted, and moist sodium aluminosilicatecrystalline material is rehydrated with a saturated saline solution foradditional removal of residual alkali and alkaline-earth cations (StepVII). The material is re-dried (Step VIII), and temporarily packaged andstored in fiber drums (Step IX) as the bulk investigational drugsubstance for shipment to the selected contractor for manufacture of thedrug product.

Example 2

The following table provides summary and manufacturing capacity for eachsynthetic and production step. TABLE 9 Step Process Step I Dissolutionof Aluminum into Sodium Hydroxide Step Ia Transfer Truck Tank Fillingand Reaction Process Step II Synthesis of Crude Crystalline SubstanceStep IIa Maturation and Drying of the Sodium Aluminosilicate Step IIISize Reduction and Selection of the Sodium Aluminosilicate Step IVTemporary Packaging and Transfer for Second Size Selection Step V SecondSize Selection of Sodium Aluminosilicate Step VI Clarification of SodiumAluminosilicate Step VII Regeneration into the Sodium form ofAluminosilicate Step VIII Drying of the Regenerated SodiumAluminosilicate Step IX Temporary Packaging and Storage of Bulk DrugSubstance

Example 3

Three particle size analyses were performed on the CR-100 zeolitemanufactured by Mineral-Right, Inc. The raw data are shown in the tablebelow. FIG. 1 shows a graphic representation of the data. TABLE 10 USStd. Pre- Post- Sieve Size regeneration (%) regeneration (%) Bed #7 800.525 1.24 100 4.65 12.36 120 43.81 44.57 140 37.15 30.52 170 11.79 8.65230 0.9 1.21 325 0.22 0.37 Pan 0.43 0.12 Bed #10 80 1.17 2.34 100 4.2418.12 120 41.4 38.6 140 38.1 29.73 170 12.11 8.83 230 1.05 1.06 325 0.340.3 Pan 0.62 0.04 Bed #11 80 0.64 0.72 100 9.38 5.37 120 35.33 39.22 14034.7 36.57 170 15.4 16.28 230 2.45 3.42 325 0.67 0.31 Pan 0.64 0.1

“Pan” in the table refers to the bottommost item in the vertical seriesof sieves which is a solid bottom designed to collect all particles,regardless of size, that pass through the smallest sieve, which isgenerally the sieve second to the bottom. Pre- and post-regenerationrefers to the particle size distribution before and after exposure to asaturated brine solution of USP salt. Only the post-regeneration productis envisioned to be used clinically. Particle size distributions maychange minimally or substantially with use of other counterions such aspotassium, calcium and others cited above.

Example 3

An experiment was performed to measure sodium aluminosilicate binding ofundesirable ions, especially heavy metals, from man. The sodiumaluminosilicate was manufactured according to the previously describedmanufacturing process. A man, weighing approximately 90 kilograms,orally self-administered a size 0 conventional pharmaceutical-grade hardgelatin capsule containing approximately 500 milligrams of sodiumaluminosilicate (CR-100, manufactured by Mineral-Right, Inc.,Phillipsburg, Kans.). The capsule was ingested with approximately 200milliliters of tap water and was immediately swallowed. The subject didnot complain of any adverse gastrointestinal effects such asconstipation, diarrhea, pain, bloating, nausea, vomiting, or bloodystools. The sodium aluminosilicate remained in the subject forapproximately 24 hours until the subject spontaneously experienced abowel movement and produced a well-formed brown stool. This material wascollected (before it was deposited into toilet and flushed) manuallywith clean, washed rubber gloves and was visually inspected for smallwhite specks of sodium aluminosilicate material.

Specks of white, granular material that was observed in the stool wascarefully teased out by the use of fine plastic tweezers, briefly dippedin deionized water to wash off any potentially contaminating fecalmaterial, and placed in a plastic container that had been previouslywashed with deionized water and air dried. The amount of sodiumaluminosilicate that was recovered was approximately 50 mg. The sodiumaluminosilicate collected from the stool (designated “After” in thetable below) and sodium aluminosilicate from the same manufacturingprocess that had not been administered to the subject (designated“Before” in the table below) were analyzed for metallic ion content withatomic absorption spectrophotometry.

The following tabulated results were noted for sodium aluminosilicatemanufactured by the method described above with the exception that thematerial was not fully regenerated with sodium and extensively clarifiedwith deionized water. The table thus reflects analysis of sodiumaluminosilicate following passage through the human gastrointestinaltract. TABLE 11 mg/kg (ppm) Practical Difference quantification betweennew Cation/Anion limit* “new” “used” and used aluminum 2,400 540,000420,000 antimony 0.7 nd nd arsenic 7.0 nd nd barium 3.5 9.3 5.8beryllium 0.7 0.8 nd bismuth 1.1 nd nd boron 50 nd nd cadmium 0.8 nd ndcalcium 560 14,000 2,800 chromium 1.5 nd nd cobalt 1.0 nd nd copper 2.710 13 iron 1,300 nd nd lead 1.8 nd 4.7 lithium 3.4 3.7 nd magnesium 3503,200 1,405 manganese 14.0 nd nd mercury 0.3 nd nd molybdenum 0.4 nd ndnickel 2.4 nd nd ammonia nitrogen 5 nd nd (mg/L) potassium 150 3,30016,000 selenium 12 nd nd silicon 8.4 730 1,900 silver 0.3 nd nd sodium410 63,000 290,000 strontium 8.4 170 72 thallium 1.3 nd nd tin 0.1 0.20.4 titanium 5.1 18 19 vanadium 1 nd nd zinc 21 nd 41*(lowest quantifiable limit of the instrument)

Lead was found in greater concentration after the aluminosilicate hadtransited the gastrointestinal tract. The sodium aluminosilicatemanufactured by Mineral-Right, Inc. may therefore be used as atherapeutic agent for removal of lead in patients with abnormally highlevels or toxic burdens of lead. The subject of this experiment wastested for elevated blood lead level. The subject's blood lead level was7.5 μg/dL which is within normal limits of <10 μg/dL. Sodiumaluminosilicate thus possesses utility in treating lead poisoning, andother metals with toxic effects, given that the sodium aluminosilicatewas able to extract the toxic metal from an individual who was notsuffering from lead poisoning. The same conclusion applies to copperpoisoning, which occurs spontaneously though rarely as a clinical entityknown as Wilson's disease or hepatolenticular degeneration.

Example 4 Sorbitol Verses Sorbitol+Zeolite Ammonia Removal Study

CR-100 is used through out this study. The study compares Sorbitoleffect on ammonia to Sorbitol with 2 Zeolite partical sizes, pan, andstandard fines. Ammonia challenge solution is approx. 100 Mg/L (100P.P.M.). Sample # 1 Sample # 2 Sample # 3 Sample # 4 Sample # 5 10 Gr.Pan 10 Gr. Fines 20 Gr. Pan 20 Cr. Fines Control; no crystal 100 ML.Same Same Same Same Sorbitol 100 ML. 95 Same Same Same Same P.P.M. NH4

Each sample is weighed dry, then wetted and added to the 100 mL sorbitolsolution spiked with 95 ppm ammonia. The experiment took place in a 250mL Erlenmeyer flask that was shaken overnight and tested for ammonia thenext morning. The concentration of the ammonia in the solution is shownbelow for each sample. Sample # 1 Sample # 2 Sample # 3 Sample # 4Sample # 5 2 P.P.M 2 P.P.M 1 P.P.M 2 P.P.M 90 P.P.M.

All publications and patent applications cited in this specification areherein incorporated by reference as if each individual publication orpatent application were specifically and individually indicated to beincorporated by reference.

The invention has been described in some detail by way of illustrationand example for purposes of clarity of understanding. However thedescription is not meant to limit the scope of the claims. The inventionbeing thus described, it will be apparent to those skilled in the artthat the same may be varied in many ways without departing from thespirit and scope of the invention. Such variations are included withinthe scope of the following claims.

1. A method of treating, preventing, or palliating elevated human bloodlead levels, comprising administering to a human in need thereof apharmaceutical formulation comprising a synthetic sodium aluminosilicatezeolite and a pharmaceutically acceptable adjuvant, wherein: (a) thesynthetic sodium aluminosilicate is particulate and at least 90% of theparticles are of particle size from about 90 μm to about 150 μm; (b) theformulation is administered in doses of about 10 mg to about 1000 mgsodium aluminosilicate.
 2. The method of claim 1, wherein at least about95% of the particles are of particle size from about 90 μm to about 150μm.
 3. The method of claim 1, wherein the formulation is from about 50%(w/w) to about 95% (w/w) water.
 4. The method of claim 1, wherein theformulation is a capsule or tablet administered enterally.
 5. The methodof claim 1, wherein the human is suffering from chronic lead poisoning.6. The method of claim 1, wherein the human has an elevated blood leadlevel.
 7. The method of claim 1, wherein the human has a blood leadlevel of at least about 10 μg/L.
 8. The method of claim 1, wherein thehuman is between about 2 and about 15 years of age.
 9. The method ofclaim 1, wherein the human is about 6 years of age or younger.
 10. Themethod of claim 1, wherein the formulation further comprises abacteriostat.
 11. A method of treating, preventing, or palliatingelevated human blood ammonia levels, comprising administering to a humanin need thereof a pharmaceutical formulation comprising a syntheticsodium aluminosilicate zeolite and a pharmaceutically acceptableadjuvant, wherein: (a) the synthetic sodium aluminosilicate isparticulate and at least 90% of the particles are of particle size fromabout 90 μm to about 150 μm; (b) the formulation is from about 50% (w/w)to about 95% (w/w) water; and (c) the formulation is administered indoses of about 2 g to about 15 g sodium aluminosilicate.
 12. The methodof claim 11, wherein at least about 95% of the particles are of particlesize from about 90 μm to about 150 μm.
 13. The method of claim 11,wherein the human is suffering from hepatic encephalopathy or cirrhosisof the liver.
 14. The method of claim 11, wherein the human has ahistory of liver failure.
 15. The method of claim 11, wherein theformulation is a liquid gel administered enterally.
 16. The method ofclaim 11, wherein the human's blood ammonia level is above normal.
 17. Amethod, comprising administering to a human in need thereof apharmaceutical formulation comprising a synthetic sodium aluminosilicatezeolite and a pharmaceutically acceptable adjuvant, wherein: (a) thesynthetic sodium aluminosilicate is particulate and at least about 95%of the particles are of particle size from about 90 μm to about 150 μm;(b) the formulation is administered in doses of from about 5 g to about12 g sodium aluminosilicate; and (c) the human has a higher than normalrisk of elevated blood levels of a toxic metal or has a higher thannormal risk of hepatic encephalopathy.
 18. The method of claim 17,wherein the human is a hospital in-patient.
 19. A pharmaceuticalformulation, comprising: (a) a particulate synthetic sodiumaluminosilicate zeolite wherein at least about 90% of the particles areof particle size from about 90 μm to about 150 μm, (b) from about 50%(w/w) to about 80% (w/w) water; and (c) a microbial preservative; and(d) a pharmaceutically acceptable adjuvant; wherein the formulationcontains from about 100 mg to about 10,000 mg by weight of sodiumaluminosilicate.